4 CKD And Nephrotic Syndrome Flashcards
What is the most common comorbid condition with CKD?
Diabetes
Continues to be the leading cause of ESRD
Gender difference in CKD prevalence
Women more commonly affected (18% vs 13%) but men tend to have more progressive course
What is the definition of CKD?
Decreased kidney function or kidney damage for 3 or more months
Glomerular filtration rate (GFR) < 60 mL/min/1.73m2
Evidence of kidney damage:
• Albuminuria*** Urine albumin:Cr ratio of ≥30 mg/g
• Abnormal imaging tests (U/S)
• Abnormal urinary sediment (ie RBC casts)
• Hx of kidney transplant
What is the best marker of kidney function?
GFR - declining GFR is the hallmark of progressive kidney disease
Serum creatinine is a poor measure of kidney function
Name the CKD Stage:
Kidney damage with normal or increased GFR (≥ 90)
Stage 1
Name the CKD Stage:
Kidney damage with mildly decreased GFR (60-89)
Stage 2
Name the CKD Stage:
Mildly-moderately decreased GFR (45-59)
Stage 3a
Name the CKD Stage:
Moderately-severely decreased GFR (30-44)
Stage 3b
Name the CKD Stage:
Severely decreased GFR (15-29)
Stage 4
Name the CKD Stage:
Kidney failure, GFR < 15
Stage 5 - add D if treated by dialysis
Name the Albuminuria classification:
ACR < 30 mg/g
Protein dipstick - negative to trace
Stage A1
Normal to mildly increased
Name the Albuminuria classification:
ACR 30-300 mg/g
Protein dipstick trace to 1+
Stage A2
Moderately increased
Name the Albuminuria classification:
ACR > 300mg/g
Protein dipstick >1+
Stage A3
Severely increased
What is important to know about measuring Albuminuria?
Must be verified by a repeated test - it has to be PERSISTENT over several months
What is the pathogenesis of CKD?
Progressive decline in the GFR typically over months to years, due to the IRREVERSIBLE DESTRUCTION OF NEPHRONS INDEPENDENT of the cause (still need to ID the cause though)
Destruction of nephrons leads to COMPENSATORY HYPERTROPHY and supranormal GFR of the remaining nephrons
Compensatory hyperfiltration leads to OVERWORK INJURY in the remaining nephrons
Progressive GLOMERULAR SCLEROSIS and INTERSTITIAL FIBROSIS
Because of the progressive nephron and GFR loss, what will you see in lab results?
Abnormalities in water, electrolyte, and pH balance
Accumulation of waste products normally excreted
Abnormalities in the production and metabolism of certain hormones (EPO, calcitriol)
What are the most common causes of CKD?
DIABETES
HTN
Glomerular disease
Polycystic kidney disease
Chronic Tubulointerstitial disorders
How should you screen patients at risk for developing CKD?
Urine albumin-to-creatinine ratio
Serum creatinine to estimate GFR (eGFR)
Who IS at risk for CKD?
60 years or older Diabetes HTN CVD FHx of kidney disease Ethnic minority Cancer Systemic infection (HIV or Hep C) Recurrent UTIs Nephrolithiasis Nephrotoxic drug exposure Autoimmune disorders Hx of AKI
What is the clinical presentation of CKD?
Dependent on underlying cause and stage
Sx develop slowly with the progressive decline in GFR
Asymptomatic in early stages
Sx may not manifest until kidney failure is far advanced
Nonspecific Sx - fatigue, for example - worry about uremic syndrome
Accumulation of metabolic waste products, or uremic toxins
Uremic syndrome
Often seen with a profound decrease in GFR (10-15 mL/min/1.73m2)
What are the SSx of uremic syndrome?
FATIGUE, MALAISE, anorexia, N/V
Pruritis, easy bruisability
Metallic taste in mouth
Shortness of breath
Dyspnea on exertion, PERICARDITIS
Restless legs, seizures, ENCEPHALOPATHY
What finding on renal U/S supports a diagnosis of CKD?
Small kidneys BL (<9-10cm) - decline in renal mass/atrophy
Although normal or enlarged kidneys may be seen as well
_________ may lead to death before the progression to ESRD
Complications of CKD
More likely to occur at later stages - why you need to ID complications early
May arise from the adverse effects of interventions used to prevent or treat
What are the main complications of CKD?
CARDIOVASCULAR DISEASE - a leading cause of death
HTN
Dyslipidemia
Anemia (b/c kidneys —> EPO)
Mineral/bone disorders
Fluid and electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypocalcemia, metabolic acidosis)
Uremia
Malnutrition (low serum albumin)
Spectrum of bone disorders that are a complication of CKD
Osteitis fibrosa cystica, adynamic bone disease, osteomalacia (bone remodeling and demineralization)
Typical pattern: hyperphosphatemia, hypocalcemia, decreased vitamin D, SECONDARY HYPERPARATHYROIDISM
CKD Mineral and Bone Disorder is often clinically detectable starting at what stage?
Stage 3 CKD
What are the keys to managing CKD?
IDENTIFY THE CAUSE
Identify and treat potentially reversible factors
Manage complications
Frequent review of meds (avoid nephrotoxic drugs, adjust drug doses when appropriate)
Identify and adequately prepare the patient in whom renal replacement therapy will be required
Reversible causes of kidney injury
Infection (do a urine culture/sensitivity)
Obstruction*** (bladder cath, renal US)
Volume depletion (BP, pulse, orthostatic measurements)
Nephrotoxic agents (drug history, recent imaging)
Heart failure (phys exam, CXR)
How do you slow the progression of CKD?
TREATMENT OF THE UNDERLYING CAUSE OF CKD
Glycemic control
BP control - ACE/ARBS to reduce proteinuria, low sodium diet
Weight management
Management of CV risk factors (statins, smoking cessation)
Why are ACE/ARBs so great for CKD patients?
RENOPROTECTIVE
Helpful in SLOWING THE PROGRESSION OF PROTEINURIC CKD (lowers albuminuria) in chronic stable patients
Inhibiting Ang II —> DILATES the EFFERENT arteriole —> reducing glomerular pressure
When are ACE/ARBs HARMFUL for CKD patients?
May see an acute reduction in GFR and hyperkalemia - ok in chronic states but a problem in acute settings
Use with caution in AKI
Contraindicated in bilateral renal artery stenosis***
What are the BP targets in patients with CKD?
In patients without proteinuria, target is <140/90
In patients WITH proteinuria, target is <130/80
Tailor BP treatment in elderly patients with CKD
When should you refer a CKD patient to nephrology?
GFR <30
Other than looking at GFR, why might we refer patients to nephrology?
To determine the cause of CKD (regardless of GFR)
Management of complications
• EPO Therapy
• CKD-MBD —> phosphate binders
• Resistant HTN
Preparation for and initiation of dialysis
Transplant evaluation
What are the options for renal replacement therapy?
Dialysis
• Hemodialysis
• Peritoneal dialysis
Kidney transplant
Indications for dialysis for CKD
Uremic symptoms
Fluid overload unresponsive to diuresis
Refractory hyperkalemia, acidosis, and hyperphosphatemia
Prepare early (GFR <30) as it takes time to set up an AV fistula
How is hemodialysis conducted?
Requires a constant flow of blood along one side of a SEMIPERMEABLE MEMBRANE with a cleansing solution, or a DIALYSATE, along the other
Diffusion and convection allow the dialysate to REMOVE UNWANTED SUBSTANCES from teh blood while adding back needed components
What are the acute complications of hemodialysis?
HYPOTENSION (25-55% of treatments) due to overfiltration
Cramps N/V HA Chest pain Back pain Itching Fever and chills
In Peritoneal Dialysis, the ________ is the dialyzer.
Peritoneal membrane
DIALYSATE is instilled into the peritoneal cavity via an in dwelling catheter
Peritoneal membrane acts as a partially permeable membrane and diffusion and osmosis drive waste products and excess fluid through the peritoneum into the dialysate
After equilibrium, the dialysate is drained, discarded, and replaced with fresh dialysate
What are the complications of peritoneal dialysis?
PERITONITIS*****
Exit site infection
Poor dialysate drainage
What is the treatment of choice for ESRD?
Kidney transplant
Improved quality of life
Reduces the mortality risk for most when compared to maintenance dialysis - but not all are medically suitable for transplant
What is chronic Tubulointerstitial disease?
Chronic disease associated with insults from an acute factor or progressive insults without any obvious acute cause
Interstitial scarring, fibrosis, and tubular atrophy leading to a progressive decrease in eGFR (CKD)
Chronic Tubulointerstitial Disease
Underlying etiologies of Chronic Tubulointerstitial Disease
Obstructive uropathy***
Reflux nephropathy***
Analgesic nephropathy
Heavy metals (lead)
Lithium
General findings of chronic Tubulointerstitial diseases
Polyuria due to inability to concentrate the urine secondary to tubular damage
Hyperkalemia due to decreased GFR as distal tubules become aldosterone resistant
U/A is nonspecific, but will have PROTEINURIA (<2g/d), broad waxy casts indicating dilated, damaged tubules
Prolonged obstruction of the urinary tract —> reduced GFR, reduced renal blood flow, and impaired tubular function
Obstructive uropathy
Tubular atrophy, interstitial fibrosis and eventually irreversible renal injury occur
Not always symptomatic depending on degree/type of obstruction
If you catch obstruction within a week or so it’s reversible
Examples of urinary tract obstructions that can lead to obstructive uropathy
Prostatic disease
Urethral calculus in a single functioning kidney
BL urethral calculi
Carcinoma of the cervix, colon, or bladder
Retroperitoneal tumors or fibrosis
What will labs/imaging show that suggests obstructive uropathy?
UA - may show hematuria, pyuria, and bacteriuria, but often benign
U/S - detect mass, hydroureter, hydronephrosis
The consequence of vesicoureteral reflux (VUR) or other urologic anomalies in early childhood
Reflux Nephropathy
Incompetent vesicoureteral sphincter —> urine can extravasated into the interstitium —> inflammatory response develops (either bacteria or normal urinary components) —> FIBROSIS occurs
When is Reflux Nephropathy usually diagnosed?
In young children with a Hx of recurrent UTIs
May go unnoticed until early adulthood, when it often presents with HTN
Dx is via RUS (showing scarring and hydronephrosis) and VCUG
CKD caused by LONG TERM, excessive consumption of analgesics, often when taken in combination medications
Analgesic Nephropathy
Example meds - acetaminophen and NSAIDs (ie excedrin)
Seen often with those who are using analgesics for chronic headaches, muscular pains, and arthritis
What do diagnostics look like for analgesic nephropathy?
UA —> hematuria, mild proteinuria, sterile pyuria (WBC but no bacteria)
CT scan —> papillary microcalcifications/necrosis
What are the key points in the treatment of Chronic Tubulointerstitial Disorders?
Identify the underlying disorder
Medical management
Relief of obstruction
Withdrawal of all analgesics
Referral to nephrology or urology
Non inflammatory damage to the glomerular capillary wall (podocyte and GBM) that can be either primary or in association with a systemic disease
Nephrotic Syndrome
Nephritic Spectrum = Diseases that present primarily with PROTEINURIA and a bland urine sediment (no cells or cellular casts
What are the distinct constellation of clinical and lab features of renal disease that make up Nephrotic Syndrome?
Nephrotic-range proteinuria (>3.5g/day), Hypoalbuminemia, Edema, Hyperlipidemia
Urine features in Nephrotic vs Nephritic Syndrome
Nephrotic = “Foamy”, oval fat bodies
Nephritic = cola-colored urine with RBC casts
Primary causes of Nephrotic Syndrome
Minimal Change Disease (MCD)
Membranous Nephropathy (MN)
Focal Segmental Glomerulosclerosis (FSGS)
Secondary causes of Nephrotic Syndrome
DIABETIC NEPHROPATHY
Amyloidosis
SSx of Nephrotic Syndrome
EDEMA (periorbital, pedal, anasarca)
ASCITES
FOAMY URINE (from excess protein)
Malaise, Anorexia, Dyspnea, Abdominal distension, Weight gain, Orthostatic hypotension from hypovolemia
Complications of Nephrotic Syndrome
Protein malnutrition
HYPERCOAGULABILITY (urinary loss of antithrombin, protein C/S, increased platelet activation)
Vitamin D deficiency and hypocalcemia (urinary loss of vitamin D binding protein)
INFECTION (urinary loss of immunoglobulins, defect in the complement cascade)
Anemia (urinary loss of EPO and transferrin)
Pathognomic urine microscopy finding suggestive of nephrotic syndrome
OVAL FAT BODY
How is Nephrotic Syndrome managed?
ACE/ARBs
Statin therapy
Loop diuretics
Sodium/fluid restriction
Anticoagulants when indicated (ie evidence of VTE)
Immunosuppressive therapy (corticosteroids, cytotoxic agents)
Nephrology referral
Most common cause of nephrotic syndrome in CHILDREN
Minimal Change Disease (MCD)
M>F, peaks at age 2 years
Most cases of MCD are idiopathic primary, but secondary MCD can be associated with…
Following an URI** (esp in children), hypersensitivity reactions (NSAIDS, bee stings), meds (lithium), malignancies (Hodgkin disease)
How does MCD usually present?
SUDDEN ONSET of edema (“Puffy appearance”) over days to a week or two
No changes on light microscopy
Primarily affects the PODOCYTE (diffuse podocyte foot process fusion) - visible on ELECTRON MICROSCOPY
What is the first line treatment for MCD?
Prednisone - works well, well tolerated
Very few patients progress to ESRD
One of the more common forms of nephrotic syndrome in the adult population, with peak around the fourth and fifth decades, M>F
Membranous Nephropathy (MN)
Most often a primary idiopathic disorder in adults
Primary MN - thought to be IMMUNE-MEDIATED, with autoantibodies directed against an antigen found on the podocytes
Secondary MN - can be due to Hep B, autoimmune diseases, thyroiditis, malignancy, drugs
How does Membranous Nephropathy present?
GRADUAL development of features of nephrotic syndrome, with a higher risk of hypercoagulable state
~20-40% will get a clot or renal vein thrombosis
Diagnosis via serology, biopsy
How do you treat Membranous Nephropathy?
Supportive
+/- immunosuppressive agents
Transplant (can be recurrent even with a transplant though)
Prognosis depends on renal function and amount of proteinuria. Adverse risk factors for male sex, older age
One of the most common causes of PRIMARY glomerular diseases in adults
Focal Segmental Glomerulosclerosis (FSGS)
A HISTOLOGIC LESION rather than a specific disease entity) accounting for 35% of all cases of idiopathic nephrotic syndrome in adults
> 70% present with nephrotic syndrome
Who is at higher risk for FSGS?
African American patients
3-4x more common in men
Typically observed in those aged 18-45 years, although no age group is exempt
What is the pathogenesis of FSGS?
Glomerular injury resulting from damage to podocytes
Sclerosis in parts (segmental) of at least one glomerulus (focal)
Less than 50% of glomeruli affected
Secondary FSGS can be due to obesity, infection, inflammations, toxins, healed previous glomerular injury, reflex nephropathy
How is FSGS treated?
Supportive
Immunosuppressive agents if primary FSGS
Disease-specific Treatment if secondary
What can indicate a poor prognosis for FSGS?
Nephrotic-range proteinuria
African American race
Renal insufficiency
Most common cause of ESRD in the US
Diabetic Nephropathy
Defined by characteristic structural and functional changes
RETINOPATHY is common - nearly universal in T1DM with nephropathy
Peak incidence is usually found in persons who have had DM for …
10-20 years
May be present at the time of diagnosis in T2DM
What is the pathogenesis of diabetic nephropathy
Direct effects of HTN and metabolic abnormalities (hyperglycemia, dyslipidemia)
Morphologic changes appear in the kidney results in increased filtration of serum proteins into the urine
Hyper filtration —> albuminuria —> slowly progressive decline in GFR
How do you treat diabetic nephropathy?
STRICT GLYCEMIC and BP CONTROL
ACE/ARBs
Statin therapy (or statin plus ezetimibe)
Dialysis and transplant when indicated
Deposition of amyloid in the glomerulus leading to proteinuria, reduced GFR, and nephrotic syndrome
Renal Amyloidosis
AL amyloidosis (previously Primary Amyloidosis) - monoclonal light chain
AA amyloidosis (previously Secondary Amyloidosis) - chronic inflammatory disease (RA) or infection
How do you screen for renal amyloidosis?
Serum and urine protein electrophoresis (SPEP and UPEP)
Looking for monoclonal light chain spikes
Prognosis varies depending on the nature, number, and extent of organ involvement
Treatment = referral to nephrology and treat underlying cause
