NEPHROLOGY Flashcards
Represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys leads to death unless the toxins are removed
end-stage renal disease
The pathophysiology of CKD involves two broad sets of mechanisms of damage:
(1) initiating mechanisms specific to the underlying etiology
(2) hyperfiltration and hypertrophy of the remaining viable nephrons
Most common inherited form of CKD
autosomal dominant polycystic kidney disease.
The normal annual mean decline in GFR with age from the peak GFR (~120 mL/min per 1.73 m2) attained during _________ is _________ , reaching a mean value of _________ at age 70
the third decade of life
~1 mL/min per year per 1.73 m2
70 mL/min per 1.73 m2
UACR above ________ in men and ________ in women serves as a marker not only for early detection of primary kidney disease, but for systemic microvascular disease as well
17 mg albumin/g creatinine
25 mg albumin/g creatinine
Serves as a well-studied screening marker for the presence of systemic microvascular disease and endothelial dysfunction
presence of albuminuria
T or F: The serum concentrations of urea and creatinine are readily measured complete surrogate markers for retained toxins in uremia
False. Accumulation of these two molecules themselves does not account for the many symptoms and signs that characterize the uremic syndrome in advanced renal failure
T or F: CKD is associated with increased systemic inflammation
True
The pathophysiology of the uremic syndrome can be divided into manifestations in three spheres of dysfunction:
(1) those consequent to the accumulation of toxins that normally undergo renal excretion;
(2) those consequent to the loss of other kidney functions,
(3) progressive systemic inflammation and its vascular and nutritional consequences
Hyponatremia is not commonly seen in CKD patients but, when present, often responds to
Water restriction
As long as water intake does not exceed the capacity for renal water clearance, the ECFV expansion will be isotonic and the patient will have a normal plasma sodium concentration
Medications that can inhibit renal potassium excretion and lead to hyperkalemia and must be cautiously used or avoided in CKD (2)
RAS inhibitors
Spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene
Certain causes of CKD can be associated with earlier and more severe disruption of potassium-secretory mechanisms in the distal nephron, out of proportion to the decline in GFR. These include conditions associated with (2)
Hyporeninemic hypoaldosteronism (diabetes) Renal diseases that preferentially affect the distal nephron (obstructive uropathy and sickle cell nephropathy)
Alkali supplementation may, in addition, attenuate the catabolic state and possibly slow CKD progression and is recommended when the serum bicarbonate concentration falls below
20–23 mmol/L
These changes that may lead to bone disease in CKD start to occur when the GFR falls below
60 mL/min
Hyperparathyroidism stimulates bone turnover and leads to
osteitis fibrosa cystica
Bone histology shows abnormal osteoid, bone and bone marrow fibrosis, and in advanced stages, the formation of bone cysts, sometimes with hemorrhagic elements so that they appear brown in color
osteitis fibrosa cystica
Brown tumor is also known as
osteitis fibrosa cystica
A devastating condition seen almost exclusively in patients with advanced CKD that is heralded by livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts
Calciphylaxis
The optimal management of secondary hyperparathyroidism and osteitis fibrosa in CKD is
prevention
Once the parathyroid gland mass is very large, it is difficult to control the disease
These are agents that are taken with meals and complex the dietary phosphate to limit its GI absorption
phosphate binders such as calcium acetate, calcium carbonate, sevelamer and lanthanum
Non-calcium-containing polymers that also function as phosphate binders; they do not predispose CKD patients to hypercalcemia and may attenuate calcium deposition in the vascular bed (2)
sevelamer and lanthanum
Enhance the sensitivity of the parathyroid cell to the suppressive effect of calcium, and produces a dose-dependent reduction in PTH and plasma calcium concentration in some patients
calcimimetic drugs such as cinacalcet
Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommend a target PTH level between
150 and 300 pg/mL
Very low PTH levels in CKD are associated with these conditions (3)
Adynamic bone disease
Fracture
Ectopic calcification
The leading cause of morbidity and mortality in patients at every stage of CKD
Cardiovascular disease
The CKD-related risk factors in the increased prevalence of cardiovascular disease are (6)
anemia hyperphosphatemia hyperparathyroidism increased FGF-23 sleep apnea generalized inflammation
The largest increment in cardiovascular mortality rate in dialysis patients is associated with (2)
congestive heart failure and sudden death
2 strongest risk factors for cardiovascular morbidity and mortality in patients with CKD that are thought to be related primarily, but not exclusively, to prolonged hypertension and ECFV overload
Left ventricular hypertrophy and dilated cardiomyopathy
The absence of hypertension in CKD may signify
poor left ventricular function
T or F, The use of exogenous erythropoiesis-stimulating agents do not have effect on the blood pressure
False. It can increase blood pressure and the requirement for antihypertensive drugs
The overarching goal of hypertension therapy in CKD is to
prevent the extrarenal complications of high blood pressure, such as cardiovascular disease and stroke
In CKD patients with diabetes or proteinuria >1 g per 24 h, blood pressure should be reduced to
<130/80 mmHg
First line of therapy in the management of hypertension in CKD
salt restriction
Antihypertensive drugs that appear to slow the rate of decline of kidney function in a manner that extends beyond reduction of systemic arterial pressure and that involves correction of the intraglomerular hyperfiltration and hypertension
ARBs and ACEi
Chest pain with respiratory accentuation, 2117 accompanied by a friction rub, is diagnostic of
pericarditis
T or F: In patients with uremic pericarditis/effusion, hemodialysis should be performed with heparin
False. Because of the propensity to hemorrhage in pericardial fluid.
Type of anemia in CKD
normochromic, normocytic
Anemia in CKD can be observed in what stage of CKD
Stage 3
Anemia in CKD is universal in what stage of CKD
Stage 4
The primary cause of anemia in CKD
insufficient production of EPO
Current practice in management of CKD is to target a hemoglobin concentration of
100–115 g/L
Coexistence of bleeding disorders and a propensity to thrombosis is unique in patients with
CKD
Subtle clinical manifestations of uremic neuromuscular disease usually become evident at what stage of CKD
Stage 3
Peripheral neuropathy usually becomes clinically evident after the patient reaches what stage of CKD
stage 4 CKD
Characterized by ill-defined sensations of sometimes debilitating discomfort in the legs and feet relieved by frequent leg movement
restless leg syndrome
T or F: Evidence of peripheral neuropathy without another cause is an indication for starting renal replacement therapy
True
A urine-like odor on the breath, derives from the break- down of urea to ammonia in saliva and is often associated with an unpleasant metallic taste
Uremic fetor
A class of drugs that result in glucose lowering, accompanied by striking reductions in kidney function decline and in cardiovascular events
SGLT-2 inhibitors
In advanced CKD, even on dialysis, patients may become more pigmented, and this is felt to reflect the deposition of retained pigmented metabolites called
urochromes
Although many of the cutaneous abnormalities in CKD improve with dialysis, this particular manifestation is often tenacious
pruritus
Pruritus in CKD may be caused by this electrolyte abnormality
hyperphosphatemia
A skin condition unique to CKD patients consists of progressive subcutaneous induration, especially on the arms and legs
nephrogenic fibrosing dermopathy
seen in patients exposed to gadolinium contrast of MRI
Stage of CKD that is contraindicated for exposure with gadolinium contrast
Stage 4-5
Stage 3 - precaution or minimize exposure
The most useful imaging study in evaluation of CKD
Renal utrasound
CKD causes with normal or increased kidney size on ultrasound (4)
DM nephropathy
Amyloidosis
HIV nephropathy
Polycystic kidney disease
_____________ that has reached some degree of renal failure will almost always present with enlarged kidneys
Polycystic kidney disease
In the patient with bilaterally small kidneys, renal biopsy is not advised because (3)
(1) it is technically difficult and has a greater likelihood of causing bleeding and other adverse consequences
(2) there is usually so much scarring that the underlying disease may not be apparent
(3) the window of opportunity to render disease-specific therapy has passed
Contraindications to kidney biopsy (4)
bilaterally small kidneys uncontrolled hypertension active urinary tract infection bleeding diathesis (including ongoing anticoagulation) severe obesity
favored approach for kidney biosy
Ultrasound-guided percutaneous biopsy
In the CKD patient in whom a kidney biopsy is indicated (e.g., suspicion of a concomitant or super-imposed active process such as interstitial nephritis or in the face of accelerated loss of GFR), the bleeding time should be measured, and if increased,_________ should be administered immediately prior to the procedure
desmopressin
or brief run of HD without heparin
The most important initial diagnostic step in approach to kidney disease management
to distinguish newly diagnosed CKD from acute or subacute renal failure
Among the calcium channel blockers, ______ and_______ may exhibit superior antiproteinuric and renoprotective effects
diltiazem and verapamil
Two human kidneys harbor nearly how many glomerular capillary tufts
1.8 million
The glomerular capillaries filter how many liters of plasma water
120–180 L/d
Humans with normal nephrons excrete on average how many mg of albumin in daily voided urine
8–10 mg
Persistent glomerulonephritis that worsens renal function is always accompanied by (3)
interstitial nephritis
renal fibrosis
tubular atrophy
T or F: Renal failure in glomerulonephritis best correlates histologically with the type of inciting glomerular injury
False. It best correlates histologically with the appearance of tubulointerstitial nephritis rather than with the type of inciting glomerular injury
Glomerular diseases often present as microscopic hematuria except for these 2 conditions wherein gross hematuria is common.
IgA nephropathy
sickle cell disease
Microalbuminuria is how much albumin in the urine?
30–300 mg/24 h
Frank proteinuria is how much albumin in the urine?
> 300 mg/24 h
Sustained proteinuria value
> 1–2 g/24 h
Foaming urine on voiding is indicative of
proteinuria
Class of proteinuria that is nonsustained, generally <1 g/24 h
benign proteinuria
sometimes called functional or transient proteinuria
caused by fever, exercise, obesity, sleep apnea, emotional stress, and congestive heart failure
Proteinuria only seen with upright posture
orthostatic proteinuria
benign prognosis
T or F: In children with minimal change disease (MCD), the proteinuria is non-selective and composed of albumin and a mixture of other serum proteins
False. selective, composed largely of albumin
Proteinuria in most adults with glomerular disease is nonselective, containing albumin and a mixture of other serum proteins
Glomerular syndrome producing 1–2 g/24 h of proteinuria, hematuria with red blood cell casts, pyuria, hypertension, fluid retention, and a rise in serum creatinine associated with a reduction in glomerular filtration
acute nephritic syndrome
If glomerular inflammation causes the serum creatinine rises quickly, particularly over a few days, this acute nephritis is called
rapidly progressive glomerulonephritis (RPGN)
Pathologic equivalent of the clinical presentation of RPGN
crescentic glomerulonephritis
When patients with RPGN present with lung hemorrhage from Goodpasture’s syndrome, antineutrophil cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis, lupus erythematosus, or cryoglobulinemia, they are often diagnosed as
pulmonary-renal syndrome
Describes the onset of heavy proteinuria (>3.0 g/24 h), hypertension, hypercholesterolemia, hypoalbuminemia, edema/anasarca, and microscopic hematuria
Nephrotic syndrome
Only large amounts of proteinuria (>3.0 g/24 h) are present without clinical manifestations
nephrotic-range proteinuria
Describes patients with vascular injury producing hematuria and moderate proteinuria
Glomerular–vascular syndrome
Affected individuals can have vasculitis, thrombotic microangiopathy, antiphospholipid syndrome, or, more commonly, a systemic disease such as atherosclerosis, cholesterol emboli, hypertension, sickle cell anemia, and autoimmunity
The most common infectious causes of glomerulonephritis throughout the world (2)
subacute bacterial endocarditis
malaria and schistosomiasis
closely followed by HIV and chronic hepatitis B and C
The kidney biopsy uses this stain to assess cellularity and architecture
hematoxylin and eosin (H&E)
The kidney biopsy uses this stain to stain carbohydrate moieties in the membranes of the glomerular tuft and tubules
periodic acid–Schiff (PAS)
The kidney biopsy uses this stain to enhance basement mem- brane structure
Jones-methenamine silver
The kidney biopsy uses this stain for amyloid deposits
Congo red
The kidney biopsy uses this stain to identify collagen deposition and assess the degree of glomerulo- sclerosis and interstitial fibrosis
Masson’s trichrome
Ideal number of glomeruli that are reviewed individually for discrete lesions in kidney biopsy
20
How many percent of glomeruli is involved in focal lesion? diffuse lesion?
<50%
>50%
When cells in the capillary tuft proliferate, it is called
endocapillary
when cellular proliferation extends into Bowman’s space
extracapillary
formed when epithelial podocytes attach to Bowman’s capsule in the setting of glomerular injury
Synechiae
develop when fibrocellular/ fibrin collections fill all or part of Bowman’s space
crescents
acellular, amorphous accumulations of proteinaceous material throughout the tuft with loss of functional capillaries and normal mesangium in the glomerulus
sclerotic glomer- uli
Histopathologic finding that is an ominous sign of irreversibility and progression to renal failure
Interstitial fibrosis
prototypical for acute endocapillary proliferative glomerulonephritis
Poststreptococcal glomerulonephritis
PSGN is common in what ages
2-14 years old
Infection prior to development of PSGN and the cause
Skin and throat infections with particular M types of streptococci (nephritogenic strains) antedate glomerular disease
Post- streptococcal glomerulonephritis due to impetigo develops ______ after skin infection and ________ after streptococcal pharyngitis
2–6 weeks
1–3 weeks
On renal biopsy, this condition demonstrates hypercellularity of mesangial and endothelial cells, glomerular infiltrates of polymorphonuclear leukocytes, granular subendothelial immune deposits of IgG, IgM, C3, C4, and C5–9, and subepithelial deposits (which appear as “humps”)
poststreptococcal glomerulonephritis
Acute nephritic syndrome with hematuria, pyuria, red blood cell casts, edema, hypertension, and oliguric renal failure, and manifests as headache, malaise, anorexia, and flank pain
PSGN
Increased titers of these antibodies can help confirm the diagnosis of PSGN (3)
ASO (30%)
anti-DNAse (70%)
antihyaluronidase antibodies (40%)
Kidneys have subcapsular hemorrhages with a “flea-bitten” appearance, and microscopy on renal biopsy reveals focal proliferation around foci of necrosis associated with abundant mesangial, subendothelial, and subepithelial immune deposits of IgG, IgM, and C3
Subacute bacterial endocarditis
Predominant organism causing glomerulonephritis in subacute bacterial endocarditis
Staphylococcus
The most common clinical sign of renal disease in lupus nephritis
proteinuria
Antibodies that correlate best with the presence of renal disease in lupus
Anti-dsDNA
the only reliable method of identifying the morphologic variants of lupus nephritis
renal biopsy
Class of lupus nephritis with minimal mesangial
Class I
Class of lupus nephritis with normal histology with mesangial deposits
Class I
Class of lupus nephritis with mesangial proliferation
Class II
Class of lupus nephritis with mesangial hypercellularity with expansion of the mesangial matrix
Class II
Class of lupus nephritis with focal nephritis
Class III
Class of lupus nephritis with focal endocapillary ± extracapillary proliferation with focal subendothelial immune deposits and mild mesangial expansion
Class III
Class of lupus nephritis with diffuse nephritis
Class IV
Class of lupus nephritis with diffuse endocapillary ± extracapillary proliferation with diffuse subendothelial immune deposits and mesangial alterations
Class IV
Class of lupus nephritis with membranous nephritis
Class V
Class of lupus nephritis with thickened basement membranes with diffuse subepithelial immune deposits; may occur with class III or IV lesions and is sometimes called mixed membranous and proliferative nephritis
Class V
Class of lupus nephritis with sclerotic nephritis
Class VI
Class of lupus nephritis with global sclerosis of nearly all glomerular capillaries
Class VI
Class of lupus nephritis that describes focal lesions with proliferation or scarring, often involving only a segment of the glomerulus
Class III
Class of lupus nephritis that have the most varied course
Class III
Class of lupus nephritis that describes global, diffuse proliferative lesions involving the vast majority of glomeruli
Class IV
Without treatment, this aggressive lesion has the worst renal prognosis among the classes of lupus nephritis
Class IV
Class of lupus nephritis that describes subepithelial immune deposits producing a membranous pattern
Class V
Patients with this class of lupus nephritis are predisposed to renal-vein thrombosis and other thrombotic complications
Class V
Lupus patients with this class of lupus nephritis have >90% sclerotic glomeruli and ESRD with interstitial fibrosis
Class VI
When do you do renal transplantation in renal failure from lupus?
Usually performed after ~6 months of inactive disease
When anti-GBM disease present with lung hemorrhage and glomerulonephritis, they have a pulmonary-renal syndrome called
Goodpasture’s syndrome
The target epitopes for the anti-GBM disease lie in the quaternary structure of
α3 NC1 domain of collagen IV
T or F: In Goodpasture’s syndrome, hemoptysis is largely confined to smokers
True
T or F: In Goodpasture’s sydrome, those who present with lung hemorrhage as a group do better than older populations who have prolonged, asymptomatic renal injury
True
presentation with oliguria is often associated with a particularly bad outcome
Renal biopsies typically show focal or segmental necrosis that later, with aggressive destruction of the capillaries by cellular proliferation, leads to crescent formation in Bowman’s space
Goodpasture’s syndrome / anti-GBM disease
Prognosis at presentation of anti-GBM disease is worse if (4)
- > 50% crescents on renal biopsy with advanced fibrosis
- serum creatinine is >5–6 mg/dL
- oliguria is present
- need for acute dialysis
In the management of Goodpasture’s syndrome, aside from dialysis, patients with advanced renal failure who present with hemoptysis should still be treated for their lung hemorrhage with
Plasmapheresis
can be life-saving
8-10 treatments
accompanied by oral prednisone and cyclophosphamide in the first 2 weeks
It is classically characterized by episodic hematuria associated with the deposition of IgA in the mesangium
IgA nephropathy
Henoch-Schönlein purpura is distinguished clinically from IgA nephropathy by (4)
- prominent systemic symptoms
- a younger age (<20 years old)
- preceding infection
- abdominal complaints.
An immune complex–mediated glomerulonephritis defined by the presence of diffuse mesangial Ig deposits often associated with mesangial hypercellularity
IgA nephropathy
In IgA nephropathy, IgA deposited in the mesangium is typically polymeric and of what subclass
IgA1
Recurrent episodes of macroscopic hematuria during or immediately follow- ing an upper respiratory infection often accompanied by proteinuria or persistent asymptomatic microscopic hematuria
IgA nephropathy
T or F: IgA nephropathy is a benign disease for the majority of patients
True
Renal failure seen in how many percent of patients with IgA nephropathy over 20–25 years
25–30%
Treatment of IgA nephropathy
ACE inhibitors
steroid and immunosuppressive therapy have conflicting results in the studies
Tonsillectomy and fish oil have also been suggested in small studies to benefit select patients
The 2 types of antibodies in ANCA small-vessel vasculitis
anti-proteinase 3 (PR3)
anti-myeloperoxidase (MPO)
Vasculitis syndromes that are ANCA-positive and have a pauci-immune glomerulonephritis with few immune complexes in small vessels and glomerular capillaries (4)
Granulomatosis with polyangiitis
Microscopic polyangiitis
Churg-Strauss syndrome
Renal-limited vasculitis
Induction therapy of ANCA small-vessel vasculitis (3)
Glucocorticoids
Rituximab or cyclophosphamide
Recommended treatment in rapidly progressive renal failure or pulmonary hemorrhage in ANCA small-vessel vasculitis
Plasmapheresis
Patients with this disease classically present with fever, purulent rhinorrhea, nasal ulcers, sinus pain, polyarthralgias/arthritis, cough, hemoptysis, shortness of breath, microscopic hematuria, and 0.5–1 g/24 h of proteinuria; occasionally there may be cutaneous purpura and mononeuritis multiplex
Granulomatosis with Polyangiitis
Biopsy of involved tissue will show a small-vessel vasculitis and adjacent noncaseating granulomas.
Granulomatosis with Polyangiitis
Renal biopsies during active disease demonstrate segmental necrotizing glomerulonephritis without immune deposits and have been classified as focal, mixed, crescentic or sclerotic
Granulomatosis with Polyangiitis
Small-vessel vasculitis that is more common in patients exposed to silica dust and those with α1-antitrypsin deficiency, which is an inhibitor of PR3
Granulomatosis with Polyangiitis
Αmong the ANCA small-vessel vasculitis, relapse is most common in
Granulomatosis with Polyangiitis
Clinically, these patients look somewhat similar to those with granulomatosis with polyangiitis, except they rarely have significant lung disease or destructive sinusitis
Microscopic Polyangiitis
Small-vessel vasculitis is associated with peripheral eosinophilia, cutaneous purpura, mononeuritis, asthma, and allergic rhinitis, often accompanied by hypergammaglobulinemia, elevated levels of serum IgE, or the presence of rheumatoid factor
Churg-Strauss Syndrome
Lung inflammation, including fleeting cough and pulmonary infiltrates, often precedes the systemic manifestations of this small-vessel vasculitis by years; lung manifestations are rarely absent
Churg-Strauss Syndrome
Small-vessel vasculitis and focal segmental necrotizing glomerulonephritis can be seen on renal biopsy, usually absent eosinophils or granulomas
Churg-Strauss Syndrome
defined morphologically with dense deposits forming ribbons in the GBM
dense deposit disease
sometimes called mesangiocapillary glomerulonephritis or lobar glomerulonephritis
membranoproliferative glomerulonephritis
It is an immune-mediated glomerulonephritis characterized by thickening of the GBM with mesangioproliferative changes; 70% of patients have hypocomplementemia
membranoproliferative glomerulonephritis
MPGN that is commonly associated with persistent hepatitis C infections, autoimmune diseases like lupus or cryoglobulinemia, or neoplastic diseases
Type I
The most proliferative of the three types of MPGN
Type I
Shows mesangial proliferation with lobular segmentation on renal biopsy and mesangial interposition between the capillary basement membrane and endothelial cells, producing a double contour sometimes called tram-tracking
Type I MPGN
Low serum C3 and a dense thickening of the GBM containing ribbons of dense deposits and C3
type II MPGN, dense deposit disease
Classically, the glomerular tuft has a lobular appearance; intramesangial deposits are rarely present and subendothelial deposits are generally absent. What type of MPGN?
Type II
MPGN that has the least proliferation and is often focal; mesangial interposition is rare, and subepithelial deposits can occur along widened segments of the GBM that appear laminated and disrupted.
Type III
MPGN that is secondary to glomerular deposition of circulating immune complexes or their in situ formation
Type I
____ percent of patients with MPGN develop ESRD 10 years after diagnosis, and ____ percent have renal insufficiency after 20 years
50%
90%
Characterized by expansion of the mesangium, sometimes associated with mesangial hypercellularity; thin, single contoured capillary walls; and mesangial immune deposits.
Mesangioproliferative glomerulonephritis
Mesangioproliferative disease may be seen in what conditions (4)
IgA nephropathy
Plasmodium falciparum malaria
Resolving postinfectious glomerulonephritis
Class II nephritis from lupus
Nephrotic syndrome classically presents with (6)
Heavy proteinuria Minimal hematuria Hypoalbuminemia Hypercholesterolemia Edema Hypertension
Minimal change disease is sometimes known as
nil lesion
Renal biopsy shows no obvious glomerular lesion by light microscopy and is negative for deposits by immunofluorescent microscopy, or occasionally shows small amounts of IgM in the mesangium
Minimal change disease
Electron microscopy demonstrates an effacement of the foot processes supporting the epithelial podocytes with weakening of slit-pore membranes.
Minimal change disease
Presents clinically with the abrupt onset of edema and nephrotic syndrome accompanied by acellular urinary sediment. Average urine protein excretion reported in 24 h is 10 g with severe hypoalbuminemia.
Minimal change disease
In minimal change disease, adults are not considered steroid-resistant until after ______ of therapy
4 months
First-line therapy for minimal change disease
Prednisone
Refers to a pattern of renal injury characterized by segmental glomerular scars that involve some but not all glomeruli
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
the clinical findings of FSGS largely manifest as
proteinuria
The pathologic changes of FSGS are most prominent in glomeruli located at the
corticomedullary junction
so if the renal biopsy specimen is from superficial tissue, the lesions can be missed, which sometimes leads to a misdiagnosis of MCD
T or F: Steroids and other immunosuppressive agents may be used in the treatment of both primary and secondary FSGS
False. There is no role for steroids or other immunosuppressive agents in secondary FSGS
Accounts for ~20% of cases of nephrotic syndrome in adults, with a peak incidence between the ages of 30 and 50 years and a male to female ratio of 2:1
Membranous glomerulonephritis
Most common cause of nephrotic syndrome in the elderly
Membranous glomerulonephritis
rare in children
Uniform thickening of the basement membrane along the peripheral capillary loops is seen by light microscopy on renal biopsy
Membranous glomerulonephritis
Immunofluorescence demonstrates diffuse granular deposits of IgG and C3, and electron microscopy typically reveals electron-dense subepithelial deposits
Membranous glomerulonephritis
T or F: The stage of glomerular disease in membranous glomerulonephritis is predictive of its progression
False. degree of tubular atrophy or interstitial fibrosis is more predictive of progression than is the stage of glomerular disease
Factors that are associated with worse prognosis in membranous glomerulonephritis (4)
Male gender
older age
hypertension
persistence of proteinuria
Nephrotic syndrome that has the highest reported incidences of renal vein thrombosis, pulmonary embolism, and deep-vein thrombosis
Membranous glomerulonephritis
The single most common cause of chronic renal failure
Diabetic nephropathy
A sensitive indicator for the presence of diabetes but correlates poorly with the presence or absence of clinically significant nephropathy
Thickening of the GBM
Some DM nephropathy patients develop eosinophilic, PAS+ nodules called
nodular glomerulosclerosis or Kimmelstiel-Wilson nodules
Microalbuminuria appears ____ years after the onset of diabetes
5–10
Feature of DM nephropathy that is a potent risk factor for cardiovascular events and death in patients with type 2 diabetes
Microalbuminuria
The absence of this condition in type 1 patients with proteinuria should prompt consideration of a diagnosis other than diabetic nephropathy
retinopathy
90% of patients with type 1 diabetes and nephropathy have diabetic retinopathy
It usually takes ____ years for DM nephropathy to reach ESRD
10–20
Specific pattern of renal injury caused by nephrotoxic light chain that causes renal failure but not heavy proteinuria or amyloidosis
cast nephropathy
Specific pattern of renal injury caused by nephrotoxic light chain that produces nephrotic syndrome with renal failure
light chain deposition disease
Result of primary fibrillar deposits of immunoglobulin light chains known as amyloid L (AL), or secondary to fibrillar deposits of serum amyloid A (AA) protein fragments
renal amyloidosis
T or F. Primary and secondary amyloidosis may both present as nephrotic syndrom
True
The treatment for primary amyloidosis that can delay the course of renal amyloidosis in about 30% of patients
melphalan
also autologous hematopoietic stem cell transplantation
Characterized by glomerular accumulation of nonbranching randomly arranged fibrils.
Fibrillary-Immunotactoid Glomerulopathy
Fibrillar/microtubular deposits of oligoclonal or oligotypic immunoglobulins and complement appear in the mesangium and along the glomerular capillary wall, and stain negative to Congo red
Fibrillary-Immunotactoid Glomerulopathy
An X-linked inborn error of globotriaosylceramide metabolism secondary to deficient lysosomal a-galactosidase A activity, resulting in excessive intracellular storage of globotriaosylceramide
Fabry’s disease
Presents in childhood in males with acroparesthesias, angiokeratoma, and hypohidrosis
Fabry’s disease
Renal biopsy reveals enlarged glomerular visceral epithelial cells packed with small clear vacuoles containing globotriaosylceramide; vacuoles may also be found in parietal and tubular epithelia
Fabry’s disease
Vacuoles of electron-dense materials in parallel arrays (zebra bodies) are seen on electron microscopy
Fabry’s disease
Fabry’s disease renal biopsy reveal features of
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Urinalysis may reveal oval fat bodies and birefringent glycolipid globules under polarized light (Maltese cross)
Fabry’s disease
Empiric and temporizing treatment for pulmonary-renal syndrome until results of testing are available (2)
plasmapheresis and methylprednisolone
Classically, patients with this condition develop hematuria, thinning and splitting of the GBMs, mild proteinuria (<1–2 g/24 h), which appears late in the course, followed by chronic glomerulosclerosis leading to renal failure in association with sensorineural deafness.
Alport’s syndrome
Approximately 85% of patients with Alport’s syndrome have an X-linked inheritance of mutations in the
α5 (IV) collagen chain on chromosome Xq22–24
15% of patients have autosomal recessive disease of the α3(IV) or α4(IV) chains on chromosome 2q35–37
Τypically have thin basement membranes on renal biopsy, which thicken over time into multilamellations surrounding lucent areas that often contain granules of varying density—the so-called split basement membrane
Alport’s syndrome
Characterized by persistent or recurrent hematuria and is not typically associated with proteinuria, hypertension, or loss of renal function or extrarenal disease
Thin basement membrane disease (TBMD)
Thin basement membrane disease (TBMD) is also known as
benign familial hematuria
it usually presents in childhood in multiple family members
Thin basement membrane disease (TBMD) is caused by a defect in what collagen
Collagen type IV
Develop iliac horns on the pelvis and dysplasia of the dorsal limbs involving the patella, elbows, and nails, variably associated with neural-sensory hearing impairment, glaucoma, and abnormalities of the GBM and podocytes, leading to hematuria, proteinuria, and FSGS
nail-patella syndrome
The syndrome is autosomal dominant, with haploinsufficiency for the LIM homeodomain transcription factor LMX1B
nail-patella syndrome
On renal biopsy there is focal sclerosing glomerulonephritis with specific lucent damage to the lamina densa of the GBM, an increase in collagen III fibrils along glomerular capillaries and in the mesangium, and damage to the slit-pore membrane, producing heavy proteinuria not unlike that seen in congenital nephrotic syndrome
nail-patella syndrome
Approximately ___ of glomeruli are normally sclerotic by age 40, rising to ___ by age 60 and ___ by age 80
10%
20%
30%
The lesion associated with HIV-associated nephropathy is
FSGS
HIV patients with FSGS typically present with nephrotic-range proteinuria and hypoalbuminemia, but unlike patients with other etiologies for nephrotic syndrome, they do not commonly have (3)
hypertension
edema
hyperlipidemia.
The lesion associated with syphilis-associated nephropathy is
membranous glomerulonephritis
Schistosoma that is most commonly associated with clinical renal disease
Schistosoma mansoni
Most common kidney stone
Calcium oxalate
2nd most common kidney stone
Calcium phosphate
T or F. A UTI in the setting of an obstructing stone requires urgent intervention to reestablish drainage
True. A UTI in the setting of an obstructing stone is a urologic emergency
The point at which the concentration product exceeds the solubility product
Supersaturation
The most clinically important inhibitor of calcium-containing stones
Urine citrate
The majority of calcium oxalate stones grow on calcium phosphate at the tip of the renal papilla forming
Randall’s plaque
Dietary factors that are associated with an increased risk of nephrolithiasis (6)
- Animal protein
- Oxalate
- Sodium
- Sucrose
- Fructose
Dietary factors associated with a lower risk of nephrolithiasis (4)
- Calcium
- Potassium
- Magnesium
- Phytate
T or F. Higher dietary calcium intake is related to a higher risk of stone formation
False. Lower risk. May be due to a reduction in intestinal absorption of dietary oxalate that results in lower urine oxalate
T or F. Supplemental calcium may increase the risk of kidney stone formation
True. May be due to the timing of supplemental calcium intake or to higher total calcium consumption leading to higher urinary calcium excretion
T or F. Dietary oxalate is a strong risk factor for kidney stone formation.
False Dietary oxalate is a weak risk factor for stone formation, BUT urinary oxalate is a strong risk factor
Vitamin C supplements will increase risk of what type of kidney stone?
Calcium oxalate
Urine output which doubly increase the risk of stone formation
<1L/day
T or F. Higher urine citrate excretion increases the risk of stone formation
False. Lower urine citrate
Urine pH that promotes uric acid stones formation
≤ 5.5
Urine pH that promotes calcium phosphate stone formation
≥6.5
Formation of this stone is not influenced by urine pH
Calcium oxalate stones
2 most common monogenic disorders that lead to stone formation
Primary hyperoxaluria
Cystinuria
Sudden onset of unilateral flank pain then intensity of pain increase rapidly often accompanied by nausea and vomiting that radiate to ipsilateral testicle in men or ipsilateral labium in women
Renal colic
2 most common presentation of acute stone event
- Renal colic
* Painless gross hematuria
Nephrolithiasis mimic acute cholecystitis if stone is at the
right ureteral pelvic junction
Nephrolithiasis mimic acute appendicitis if stone is at the
blocks the ureter as it crosses over the right pelvic brim
Nephrolithiasis mimic acute diverticulitis if stone is at the
left pelvic brim
T or F: Absence of hematuria exclude the diagnosis of stone
False
Preferred imaging and highly sensitive for nephrolitiasis
Helical computed tomography
Drugs that may increase the rate of spontaneous kidney stone passage
Alpha blocker
Indications for urologic intervention (3)
• Evidence of UTI • Low probability of spontaneous stone passage o Stone measuring ≥6 mm o Anatomic abnormality • Intractable pain
The least invasive option for nephrolithiasis
Extracorporeal shockwave lithotripsy (ESWL)
Uses shock waves generated outside the kidney body to fragment the stone
Extracorporeal shockwave lithotripsy (ESWL)
Serve as the cornerstone on which therapeutic recommendations for nephrolithisis are based
24-h urine collection
The “gold standard” diagnostic test for nephrolithiasis
Helical CT without contrast
For all kidney stone types, consistently _____ reduces the likelihood of crystal formation
diluted urine
Urine volume should be at least 2 L/d
Antihypertensive drugs that can lower urine Ca in doses higher than those used to treat HPN
Thiazide diuretic (Most commonly chlorthalidone)
The only strategy that reduces endogenous oxalate production
Avoiding high-dose Vit C supplements
Supplemental alkali that may be given to kidney stone patients (2)
potassium citrate or bicarbonate
2 main risk factors for uric acid stone formation
- Persistently low urine pH
* Higher uric acid excretion
The focus for cystine kidney stone prevention
Increasing cystine solubility
Medication that covalently binds to cystine (2)
Tiopronin
Penicillamine
Preferred medication that covalently binds to cystine
Tiopronin
AKA infection stones
Struvite
AKA triple-phosphate stones
Struvite
Struvite forms only when the upper urinary tract is infected with
urease-producing bacteria
3 bacteria that most commonly cause struvite
- Proteus mirabilis
- Klebsiella pneumoniae
- Providencia species
Urease produced by urease-producing bacteria hydrolyzes urea and may elevate the urine pH to
> 8.0
Struvite stones may grow quickly and fill the renal pelvis causing
staghorn calculi
2 management for staghorn calculi
Complete removal
Acetohydroxamic acid
Imaging that is often used for long-term follow-up of nephrolithiasis
Plain abdominal radiography (KUB)
The first tolerable and effective agent for the treatment of UTI
Nitrofurantoin
The most common manifestation of UTI
Acute cystitis
Refers to acute cystitis or pyelonephritis in nonpregnant outpatient women without anatomic abnormalities or instrumentation of the urinary tract
Uncomplicated UTI
Prevalence of UTI during the neonatal period according to sex
male>female
Prevalence of UTI after 50 years of age according to sex
male=female
Prevalence of UTI between 1-50 years of age
female > male
How many percent of women in the general population acquire at least one UTI during their lifetime
50–80%
Independent risk factors for acute cystitis (3):
- Recent use of a diaphragm with spermicide
- Frequent sexual intercourse
- History of UTI
Risk factors of UTI in healthy postmenopausal women (3):
- Sexual activity
- Diabetes mellitus
- Incontinence
Factors independently associated with pyelonephritis in young healthy women (6)
- Frequent sexual intercourse
- New sexual partner
- A UTI in the previous 12 months
- Maternal history of UTI
- Diabetes
- Incontinence
Independent risk factors of UTI recurrence in premenopausal women (5)
- Frequent sexual intercourse
- Use of spermicide
- New sexual partner
- First UTI before 15 years of age
- Maternal history of UTI
Major risk factors of recurrent UTI in postmenopausal women (2)
- History of premenopausal UTI
* Anatomic factors affecting bladder emptying
Most common cause of UTI in men
urinary obstruction secondary to prostatic hypertrophy
UTI due to lack of circumcision is due to what organism
Escherichia coli
Most common organisms causing UTI
enteric gram-negative rods (most common: E. coli)
Most common route of infection in UTI
Ascending from the urethra to the bladder
Hematogenous route is present in how many % of documented UTIs
<2%
Hematogenous route of UTI is most commonly seen in these 3 organisms
- Salmonella
- S. aureus
- Candida
The critical initial step in the pathogenesis of UTI among women
Colonization of the vaginal introitus and periurethral area with organisms from the intestinal flora
Inhibition of ureteral peristalsis and decreased ureteral tone leads to this condition which is important in the pathogenesis of pyelonephritis in pregnant women
Vesicoureteral reflux
The primary reason why UTI is predominantly an illness of young women rather than of young men
Distance of the urethra from the anus
Virulence factor of E. coli that mediate binding to specific receptors on the surface of uroepithelial cells
Surface adhesins
Virulence factor of E. coli described as hair-like protein structures that interact with a specific receptor on renal epithelial cells
P fimbriae
Virulence factor of E. coli that is important in the pathogenesis of pyelonephritis and subsequent bloodstream invasion from the kidney
P fimbriae
Play a key role in initiating E. coli bladder infection that mediate binding to mannose on the luminal surface of bladder uroepithelial cells
Type 1 pilus
The most important issue to be addressed when a UTI is suspected is the
characterization of the clinical syndrome
An indication that the upper urinary tract is involved in UTI
Unilateral back or flank pain
An indication of invasive infection of either the kidney or the prostate
Fever
Severe pyelonephritis is characterized by these clinical manifestations (5)
- High fever
- Rigors
- Nausea
- Vomiting
- Flank and/or loin pain
the main feature distinguishing cystitis from pyelonephritis
Fever
Fever in pyelonephritis typically exhibits this pattern
high spiking “picket-fence” pattern
Complication of pyelonephritis seen in patients with diabetes that present as obstructive uropathy when sloughed papillae obstruct the ureter
Acute papillary necrosis
A particularly severe form of the pyelonephritis that is associated with the production of gas in renal and perinephric tissues
Emphysematous pyelonephritis
Emphysematous pyelonephritis occurs almost exclusively in what group of patients
Diabetic patients
Occurs when chronic urinary obstruction (often by staghorn calculi) together with chronic infection causes this suppurative destruction of renal tissue
Xanthogranulomatous pyelonephritis
Causes yellow coloration of kidney with infiltration by lipid-laden macrophages
Xanthogranulomatous pyelonephritis
When to you suspect the abscess as complication of pyelonephritis?
when a patient has continued fever and/or bacteremia despite antibacterial therapy
Presents as fever, chills, dysuria, frequency, and pain in the pelvic or perineal area in men
Acute bacterial prostatitis
In women presenting with at least one symptom of UTI (dysuria, frequency, hematuria, or back pain) and without complicating factors, the probability of acute cystitis or pyelonephritis is
50%
If vaginal discharge and complicating factors are absent and risk factors for UTI are present, then the probability of UTI is close to___, and no laboratory evaluation is needed
90%
Combination of dysuria and urinary frequency (in the absence of vaginal discharge) increases the probability of UTI to
96%
Laboratory tests that provide point-of-care information for UTI
Urine dipstick test
Urinalysis
Only members of the family ______ convert nitrate to nitrite that can be detected in urine dipstick test
Enterobacteriaceae
Enough ______ must accumulate in the urine to reach the threshold of detection
Nitrite
Diagnostic gold standard for UTI
Urine culture
In symptomatic women, colony count threshold of ______ can be diagnostic of UTI
≥10^2 bacteria/mL
T or F. Men with febrile UTI for the first time should have imaging performed
True
CT or ultrasound
Microbiologic criterion for asymptomatic bacteriuria
≥10^5 bacterial CFU/mL of urine
The predominant multilocus sequence type found worldwide as the cause of multidrug-resistant UTI
E. coli ST131
previously recommended as first-line treatment for acute cystitis
TMP-SMX
Organisms that are intrinsically resistant to this nitrofurantoin (5)
- Proteus
- Pseudomonas
- Serratia
- Enterobacter
- Yeasts
T or F. Nitrofurantoin may be used in the treatment of pyelonephritis
False
Most fluoroquinolones are highly effective as short-course therapy for cystitis, except
moxifloxacin – may not reach adequate urinary levels
Rare but potentially serious adverse effects of fluoroquinolones in >60 years of age
Increased risk of Achilles tendon rupture
Widely used urinary analgesics but can cause significant nausea
Phenazopyridine
First-line therapy for acute uncomplicated pyelonephritis
Fluoroquinolones
Oral ciprofloxacin (500 mg twice daily, with or without an initial IV 400-mg dose)
UTI medications that are relatively safe in early pregnancy (3)
- Nitrofurantoin
- Ampicillin
- Cephalosporins
2 drugs of choice for UTI in pregnancy
Ampicillin
Cephalosporins
Standard of care for overt pyelonephritis in pregnancy
parenteral β-lactam therapy with or without aminoglycosides
For acute bacterial prostatitis, what is the recommended treatment and duration?
fluoroquinolone or TMP-SMX
2-4 weeks
For chronic bacterial prostatitis, what is the recommended treatment and duration?
fluoroquinolone or TMP-SMX
4-6 weeks
For recurrent bacterial prostatitis, what is the recommended treatment and duration?
fluoroquinolone or TMP-SMX
12 weeks
Treatment for xanthogranulomatous pyelonephritis
nephrectomy
Initial treatment for emphysematous pyelonephritis
Percutaneous drainage
Elective nephrectomy on follow-up
Treatment of asymptomatic bacteriuria is given only in (4)
- Pregnant women
- Persons undergoing urologic surgery
- Neutropenic patients
- Renal transplant recipients
Accepted threshold for bacteriuria to meet the definition of CAUTI
≥10^3 CFU/mL of urine
Risk factors for candiduria (3)
- ICU patients
- Those taking broad-spectrum antimicrobial drugs
- Those with underlying diabetes mellitus
Therapy for candiduria is recommended for patients who (5)
- Have symptomatic cystitis or pyelonephritis
- Neutropenia
- Undergoing urologic manipulation
- Clinically unstable
- Low-birth-weight infants
(At high risk for disseminated disease)
First-line regimen for Candida infections of the urinary tract
Fluconazole – (200–400 mg/d for 7–14 days)
Three prophylactic strategies for recurrent UTI in women
Continuous therapy (6 months)
Postcoital therapy
Patient-initiated therapy
Most common cause of bacterial cystitis
Escherichia coli
An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks’ duration, in the absence of infection or other identifiable causes
INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME
Ulcer in the bladder
Hunner lesion
How many % of interstitial cystitis/bladder pain syndrome has Hunner lesion?
≤10%
Most common site of interstitial cystitis/bladder pain syndrome
Suprapubic (80% of women) – most severe pain
In 95% of patients, bladder filling exacerbates the pain and/or bladder emptying relieves it
interstitial cystitis/bladder pain syndrome
Functional somatic syndromes that can accompany IC/BPS (3):
a. Gynecologic chronic pelvic pain
b. Irritable bowel syndrome
c. Fibromyalgia
Oral medications for interstitial cystitis/bladder pain syndrome:
a. NSAIDs
b. Amitriptyline
c. Pentosan polysulfate
Treatment of hunner lesion in interstitial cystitis/bladder pain syndrome:
Fulguration (solutions containing lidocaine, hyaluronic acid, or dimethyl sulfoxide can be instilled into the bladder)
Normal points of narrowing are common sites of urinary tract obstruction (4)
- Ureteropelvic junction
- Ureterovesical junction
- Bladder neck
- Urethral meatus
Most common cause of utinary tract obstruction in childhood
Congenital malformations
- Narrowing of the ureteropelvic junction
- Abnormal insertion of the ureter into the bladder
Most common cause of bilateral hydronephrosis in boys
Posterior urethral valves
Most common causes of urinary tract obstruction in adults (3)
- Pelvic tumors
- Calculi
- Urethral stricture
Symptom that most commonly leads to medical attention in urinary tract obstruction
Flank pain
Flank pain that occurs only with micturition is pathognomonic of
vesicoureteral reflux
Partial bilateral UTO often results in (3)
- Acquired distal renal tubular acidosis
- Hyperkalemia
- Renal salt wasting
Struvite is made of what mineral/compound?
Magnesium ammonium phosphate
Used for the diagnosis of vesicoureteral reflux and bladder neck and urethral obstructions
Voiding cystourethrography
T or F. Even in obstruction without infection, immediate surgical intervention must be done to avoid complications
False. When infection is not present, surgery is often delayed until acid-base, fluid, and electrolyte status is restored
Functional obstruction secondary to neurogenic bladder may be decreased with the combination of (2)
frequent voiding and cholinergic drugs
Duration of obstruction wherein kidney function recovery is unlikely
After 8 weeks of obstruction
Imaging performed after a prolonged period of decompression and to predict the reversibility of renal dysfunction
Renal radionuclide scan
Total body water is composed of ____ intracellular, and ____ extracellular
2/3
1/3
Extracellular fluid is composed of ___ plasma, and ___ interstitial edema
¼
3/4
Fluid is returned from the interstitial space into the vascular system through the
Lymphatic system
A parameter that represents the filling of the arterial tree and that effectively perfuses the tissues
Effective arterial blood volume
Decrease effective arterial blood volume will _____ renin release
Increase
Decreased effective arterial blood volume -> diminished renal blood flow -> translated by the renal juxtaglomerular cells (specialized myoepithelial cells surrounding the afferent arteriole) into a signal -> increased renin release
Specialized myoepithelial cells surrounding the afferent arteriole that detects diminished renal blood flow
juxtaglomerular cells
Angiotensinogen is synthesized in the
Liver
Angiotensin II has generalized vasoconstrictor properties, particularly on the
renal efferent arterioles
Aldosterone acts on the _____ by _____
Collecting tubule
Enhances sodium reabsorption and potassium excretion
RAAS effect on Na and water
Retention
Arginine vasopressin is secreted by
posterior pituitary gland
Arginine vasopressin secretion occurs in response to
increased intracellular osmolar concentration
AVP stimulates what receptors
V2 receptors
Site of action of AVP in the kidney
distal tubules and collecting ducts
Action of AVP on the kidney
increases the reabsorption of free water
Potent peptide vasoconstrictor released by endothelial cells
Endothelin-1
Elevated in patients with severe heart failure
Stimulates release of ANP
Atrial distention
ANP and BNP are stored in these sites respectively
Atrial myocytes
Ventricular myocytes
Stimulates release of BNP
When ventricular diastolic pressure rises
Effects of ANP and BNP on Na and water
Excretion of sodium and water
Augmenting glomerular filtration rate
Inhibiting sodium reabsorption in the proximal tubule
Inhibiting release of renin and aldosterone
Primary alteration in the nephrotic syndrome causing edema
diminished colloid oncotic pressure
Causes of edema in hepatic cirrhosis (4)
- Hepatic venous outflow obstruction leading to increase splanchnic blood volume
- Hepatic lymph formation
- Hypoalbuminemia
- Peripheral artery vasodilation
Multiple peripheral arteriovenous fistulae result in reduced effective systemic perfusion and effective arterial blood volume and leading enhancing edema formation in this condition
Beriberi heart disease
Edema develops or becomes intensified when famished subjects are first provided with an adequate die
Refeeding edema
