Nephrology/Urology Clinical Medicine Exam

Definition of CKD

Persistent progressive deterioration of renal function, may progress to ESRD

• Kidneys are unable to regulate volume, maintain electrolytes and acid base function, or manage endocrine/metabolic function

• MCC by DM, 2nd MCC is HTN

• uACR is the best early detection method to measure early damage

Early intervention in CKD

Intensive glucose control, early HTN control, early nephrology referral (around <30 GFR)

• Cornerstone of tx: ACE/ARB, SGLT2-i, MRAs (up and coming GLP-1)

Pathophysiology of CKD

Number of functioning nephrons decreases (d/t renal insult or dz), initially there will be compensation too preserve total GFR (hyperfiltration)→ sustained hyper filtration furthers glomerular deterioration d/t increased intraglomerular HTN through increased pressure, this result sin a progressive decline in function that disturbs all aspects of renal function

• Enlarged glomeruli with increased pressure/flow will increase capillary permeability and allow protein leakage (microalbuminuria)

Changes in CKD

• Causes of hyperfiltration: hyperglycemia, systemic HTN, increased dietary protein intake

• Chronic changes: capillary sclerosis, thickened/narrow lumens, tubular atrophy/fibrosis

• Systemic effects (uremia): fluid/electrolyte (hypervolemia, hyperkalemia, hypocalcemia), acidosis (shift of K), chronic metabolic acidosis

  • Anemia, HTN, osteodystrophy, nausea, constipation, peripheral neuropathy, pruritus, dry skin, depression, impaired cognition

Uremic syndrome

Happens due to high levels of creatinine and urea wast (extensive disease, may need tx)

• Fatigue, weakness, irritability, memory impairment, N/V, restless legs, insomnia, dysgeusia, decreased appetite, edema, SOB, pruritus, decreased libido, fertility and menstrual irregularities, neuropathy

Goals of CKD treatment

• Slow progression to preserve remaining kidney function (Decrease proteinuria, manage BP, weight loss, nephrotoxin avoidance, and optimize glucose and lipid levels)

• maintain fluid/electrolyte/nutrition balance

• Decrease uremic symptoms and complications

• Adjust drugs according to decreasing GFR

Microalbuminuria (uACR)

Indicates early glomerular damage, often prior to a GFR drop (up to 5 years prior)

• Increased risk of CV events, monitor yearly in pts at risk (HTN or DM)

• Tx with RAAS blockade (ACE/ARB, SGLT2-I, MRA)

• important measure to gauge prognosis, progression, CV mortality risk, tx guidance

• PROTEIN RESTRICT: 0.6-0.8 g/kg/day to slow CKD progression

Disease modifying treatment in CKD

ACE/ARB (first line CKD tx): dilate efferent arteries, decrease HTN and proteinuria

• May cause increase creatinine or hyperkalemia (need to monitor Cr/K+ levels)

• Goal BP is <130/80

• Creatinine may raise 30%→ continue medication

Hypertension in CKD

Most common CKD complication and 2nd leading cause of CKD

• progressive, resistant, and salt sensitive (SALT RESTRICT DIET)

• Tx: Stage 1-4: Thiazide diuretics, Stage 5: Loop diuretics + ACE/ARB ± beta blockers, Minoxidil

Clinical findings of CKD

HTN, decreased drug clearance (toxicity), hypoglycemia (insulin is not cleared), volume overload, pericarditis

Uremic encephalopathy

Pt will be ill appearing, N/V, metallic taste, pruritus, halitosis, decrease in mental status, confusion, asterixis, myoclonus, seizures

• Tx: emergent dialysis and hospital admission

• This occurs around GFR <5-10

CKD vs AKI differentiation

• Assessing for chronicity on previous labs and hx

• sudden increased of Creatinine levels or sudden eGFR drop → consider/investigate reversible causes

• U/S= small echogenic kidneys points to chronic kidney disease

• Investigate if there is a superimposed AKI on top of a chronic condition

Reversible causes of exacerbation of CKD

AKI on CKD

• UTI, nephrotoxins (NSAID, PPI, ahminoglycosides), hypovolemia/HoTNm HF, severe HTN, hypercalcemia

Diagnosis of CKD

GFR <60 for >/= 3 months OR persistent proteinuria or abnormal imaging even if GFR normal

• Creatinine (plot overtime), CBC (anemia), hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, urinary sediment/casts (urinalysis)

• Imaging: US (small echogenic kidneys), renal artery imaging (r/o RAS, vascular perfusion abml)

• Track and trends eGFR+uACR

Diabetic neuropathy in CKD

Leading cause of ESRD in the U.S.; type 1 DM usually has kidney problems within 2 years of diagnosis and Type 2 may have renal dz at diagnosis

• Hyperglycemia leads to glomerular stress and increased pressure in the kidneys, the thickened glomerular basement membrane leads to albuminuria, glomerular sclerosis and capillary damage that leads to an increase in blood pressure in the kidney (progresses to more and more excretion of albumin)

CV risk in CKD

Increase mortality risk d/t CV event in the uremic environment, increased oxidative stress and inflammation (phosphorus and calcium)

• CV risk in Stage 4 CKD often precedes ESRD (death prior to reaching ESRD), antiHTN are the cornerstones of tx

• BP should be under 130/80

Heart failure in CKD

Increased cardiac workload caused by HTN, volume overload, and anemia

• SGLT2-I improves HF and CKD, use diuretics, FLUID AND SALT RESTRICTIONS

  • fluids: output+ 500 mL

• Diastolic dysfunction is common (LVH)

• Accelerated rates of atherosclerosis and calcification= accelerated HF

DO NOT USE DIGOXIN

Pericarditis in CKD

Pleuritic chest pain, friction rib, tamponade risk (end stage dz, rare to happen if a pt is on dialysis)

• TX: hospitalization and immediate dialysis

Electrolyte imbalance in CKD

• Hyperkalemia (>7) can cause peaked T-waves and widened QRS on ECG (weakness, palpations, arrhythmia), tx urgently if ECG changes are present

  • Can cause constipation (no use of Mg/Po4 laxatives), 2g/day diet restrict, add K+ binders if needed (patiromer)

• Acid-base: metabolic acidosis (decreased renal ammonium production and decreased H+ excretion, early on is a non-anion gap

  • Tx: PO sodium bicarbonate

Ca/Phosphate/Bone changes in CKD

Hyperphosphatemia, hypocalcemia, decreased vitamin D= increased PTH→ secondary hyperparathyroidism

• increased fracture risk, osteomalacia, adynamic bone disease, osteitis fibrosa cystia

• Tx: PO phosphate binders, dietary phosphate restriction, 2ndry hyperparathyroid (Calcitrol)

Anemia in CKD

Normocytic, normochromic; decreased EPO=decreased RBC lifespan

• ESA if Hgb 9-10 g/dL→ goal 10-11 g/dL (if adequate iron) Epoetin Alfa (Epogen, Procrit)

• Ferritin >500 ng/mL use IV iron→ d/c at 700 ng/mL

• Hct goal 33-36%

Do not use ESA if there is a hx of cancer w/o oncology consult

Bleeding in CKD

Bleeding time increases even with normal platelet levels (dysfunction common); increased NO inhibits platelet aggregation

• give pre-procedural desmopressin

Itching/dyspepsia in CKD

• topical moisturizers/antihistamines

• H2 blockers (no PPI)

Stage 1 CKD

GFR >/=90 but with albuminuria or structural damage; no s/s but high risk of progression

Stage 2 CKD

GFR 60-89, mildly decreased renal function, albuminuria often present, often asymptomatic

• Tx: screen, monitor, control risk factors

Stage 3a CKD

GFR 45-59, mild/moderate renal insufficiency

• Tx: begin metabolic monitoring (Hgb, Ca, PO4, PTH, HCO3)

Stage 3b CKD

GFR 30-44, mod/sever decrease in renal function, increased risk of complications

• Tx: referral to nephrology recommended

Stage 4 CKD

GFR 15-29, severely decreased renal function, CKD typically remains asymptomatic

• Tx: prepare for RRT (dialysis education), intensify lab and medication monitoring

Stage 5 CKD/ESRD

GFR <15 or need for dialysis, dialysis or transplant required to sustain life→ may choose palliative care

• Tx: hemodialysis, peritoneal dialysis, kidney transplant, palliative care

Polycystic Kidney Disease (PCKD)

Genetic disorder (autosomal dominant) that cause numerous fluid filled cysts to grow in the kidneys; overtime enlarges the kidneys, damages tissue, and decreases function

• Risks: 1 in 800 live births, 50% will have ESRD by 60 yo, 10% of dialysis patients have PCKD, usually dx as an adult

  • PKD-1 (85% of cases)= chromosome 16, PKD-2 (15% of cases)= chromosome 4

S/S of polycystic kidney disease

Multiple b/l cysts, abdominal flank pain, microscopic or gross hematuria, more than 50% have gun prior to dx, hx of nephrolithiasis and/or UTIs

Dx of polycystic kidney disease

Kidneys may be palpable on PE, Hgb usually maintained, MRI (most sensitive)

• Genetic testing, urinalysis (hematuria and mild proteinuria)

• PKD-1: US dx (>/= 2 cysts in kidneys 30-59 yo, >/= 4 cysts in kidneys 60+ yo)

• W/O genetic history do CT for dx

Tx of polycystic kidney disease

Increased fluid intake, pain management, address cyst ruptures and infections fast and aggressively treat HTN (avoid caffeine and tobacco)

• FDA approved: Tolvapatan (vasopressor receptor antagonists)

• Pain: bed rest and analgesics (acute), cyst decompression (chronic)

• Hematuria: bed rest and fluids (recurrent bleeding may point to renal cell carcinoma)

• Infections: Fluoroquinolones/Bactrim (2 wk then PO), pain management, possible drain

• Nephrolithiasis: hydration 2-3 L daily

• HTN: ACE/ARB

• Cerebral Aneurysm: MRA screening if (+ fam hx, high risk occupation, elective sx)

• Vascular/GI: mitral valve prolapse (through cardiac evaluation), colonic diverticula

Tolvapatan

Only FDA approved tx for PCKD

• vasopressin receptor antagonist to slow volume growth and decrease in function

• Monitoring: liver toxicity and polyuria