308: APPROACH TO THE PATIENT WITH RENAL DISEASE OR NEPHRITIC SYNDROME
URINARY TRACT DISEASE • Definition: Inflammatory kidney disease
• Causes:
o Infections, drug reactions, autoimmune disease, toxins
OVERVIEW OF URINARY TRACT STRUCTURE • Features:
• Upper urinary tract: o Enlarged tender kidneys
o Kidneys, renal vasculature, renal parenchyma, and collecting o Flank/CVA tenderness
system • Classification:
• Lower urinary tract: o Anatomical: vascular, glomerular, tubulointerstitial
o Ureters, bladder, urethra o Temporal: acute, subacute, chronic
• Urine production:
o Begins as plasma ultrafiltrate in glomeruli → modified by GLOMERULONEPHRITIS (GN)
renal tubules → excretion via urethra • Symptoms:
o Hypertension, edema, oliguria/anuria
PRESENTATION OF RENAL AND URINARY TRACT DISEASE o Dyspnea, orthopnea, ascites (esp. in children)
• Disease can be: • Urinalysis:
o Asymptomatic (e.g., incidental renal mass, microhematuria) o Hematuria (microscopic or gross), proteinuria
o Nonspecific (e.g., fatigue) o Dysmorphic RBCs, PMNs, RBC casts
o Syndrome-specific (e.g., proteinuria, nephritic syndrome) • Disease timeline:
o Pathognomonic (e.g., polycystic kidney disease) o Acute: postinfectious GN, RPGN
• Discovered via: o Chronic: years of progressive damage
o Lab testing
o Imaging (incidental findings) POSTINFECTIOUS GLOMERULONEPHRITIS (PIGN)
• Evaluate renal function when: • Etiology: Group A Streptococcus (pharyngitis, impetigo)
o Systemic disease is present (e.g., diabetes mellitus → • Timing: 10 days–3 weeks post-infection
screen for albuminuria) • Pathogenesis: Complement-mediated immune complex GN
o Known risk factors (e.g., lithium, lead, aniline dyes) • Labs: Low serum C3
• Clinical clues: Previous sore throat or skin infection
DIAGNOSTIC APPROACH TO RENAL DISEASE
• Differentials:
• Avoid premature random testing o Infection-related GN: e.g., MRSA abscess; ongoing infection
• Use structured approach: o IgA nephropathy (synpharyngitic hematuria):
o History: family history, toxins, birth weight, medication use ▪ Gross hematuria concurrent with infection
o Physical examination ▪ Normal C3
o Basic labs: urinalysis, blood chemistries
▪ Associations: celiac disease, RA, reactive arthritis,
• Determine: ankylosing spondylitis
o Region involved (glomeruli vs tubules) ▪ More common in Asians
o Time course (acute vs chronic)
• Glomerular dysfunction → hallmark: albuminuria RAPIDLY PROGRESSIVE GN (RPGN)
• Tubular dysfunction → electrolyte disturbances, issues with • Definition: Crescentic GN with rapid GFR decline
dilution/concentration • Histology: Crescents (proliferation of parietal epithelial cells,
• Chronicity causes overlap: inflammatory cells)
o Glomerular → tubular-interstitial scarring • Diffuse involvement: >50% glomeruli → high risk of sclerosis
o Tubular → secondary glomerular damage
• Clinical:
CASE EXAMPLE: CYSTINOSIS (Fanconi’s Syndrome in Children)
o Hemoptysis, epistaxis, sinusitis (pulmonary-renal syndrome)
• Early signs: • Types:
o Salt-wasting, polyuria, dehydration, poor growth o Pauci-immune GN (ANCA-positive):
o Hypokalemia, RTA, glycosuria, phosphaturia → renal rickets ▪ c-ANCA: proteinase-3 (granulomatosis with
polyangiitis)
• Later progression: ▪ p-ANCA: MPO (microscopic polyangiitis)
o Albuminuria, decreased GFR, retained K+ and phosphate
o Anti-GBM disease:
o Metabolic acidosis due to ↓ NH4⁺ production
▪ Renal-limited or Goodpasture syndrome (renal +
o Hypertension and edema
lung hemorrhage)
o Anemia (↓ erythropoietin)
o Nonspecific symptoms: weakness, fatigue, acidosis, carnitine ▪ Young males, smokers
deficiency o Immune complex RPGN:
▪ Low C3: lupus, cryoglobulinemia
• Specific finding:
o Photosensitivity from corneal cystine crystals ▪ Cryoglobulinemia: high RF, low C4, hepatitis C or
myeloma
• Differentials: ▪ IgA vasculitis (Henoch-Schönlein purpura):
o Hepatomegaly may suggest glycogen storage disease purpura, GI bleed, arthralgia, pulmonary
hemorrhage
MAJOR CLINICAL SYNDROMES IN RENAL DISEASE
▪ C3 deposits on biopsy but normal serum C3
,TUBULOINTERSTITIAL NEPHRITIS (TIN) o Generalized edema
o Foamy urine
ACUTE INTERSTITIAL NEPHRITIS (AIN) • Proteinuria ≠ Nephrotic Syndrome (NS)
• Causes: Drugs (most common), infection, autoimmunity • Microalbuminuria (MALB):
• Timing: 1 day–2 weeks post-drug exposure o First sign of glomerular damage in diabetes mellitus (DM)
• Drugs: o Defined as 30–300 mg/day of albumin excretion
o NSAIDs, beta-lactams, PPIs, sulfa drugs (e.g., o Detected by radioimmunoassay (not dipstick)
sulfamethoxazole), rifampin o Predicts progression to NS and renal failure
o CPIs (immune checkpoint inhibitors) o Associated with:
• Symptoms: ▪ Retinopathy (shared microvascular pathology)
o Fever, rash, eosinophilia ▪ Hypertension, obesity, poor glucose control
o Polyuria, nephrogenic diabetes insipidus, electrolyte ▪ Nephrectomy, hepatitis C
abnormalities ▪ APOL1 gene mutations (especially in African
• Urinalysis: ancestry, e.g., FSGS)
o Pyuria, eosinophiluria, WBC casts • Subnephrotic albuminuria:
o Activated T-cells, plasma cells on Giemsa stain o Focal glomerular diseases (<50% glomeruli involvement)
• Nephrotic proteinuria:
GRANULOMATOUS INTERSTITIAL NEPHRITIS o Involves most glomeruli (diffuse involvement)
• Drugs: Rifampin, CPIs • Dipstick proteinuria:
• Infections: TB (caseating granulomas), sarcoidosis (noncaseating) o Detects acidic proteins (like albumin)
• Location: Begins near glomeruli in TB o Cannot detect kappa/lambda light chains (multiple myeloma)
o Detectable albumin on dipstick = overt proteinuria
SYSTEMIC AND AUTOIMMUNE TIN • Overflow proteinuria:
• Diseases: o Due to low molecular weight proteins (e.g., light chains)
o SLE, Sjögren’s syndrome, ANCA vasculitis o Cross glomerular barrier freely
o TINU (Tubulointerstitial nephritis + uveitis) o Can damage glomeruli (e.g., AL amyloidosis, light-chain
nephropathy)
NONINFLAMMATORY INTERSTITIAL NEPHROPATHY • Tubular proteinuria:
o Caused by proximal tubular dysfunction
TOXIN-RELATED o β-2 microglobulin is the main protein
• Ifosfamide: Fanconi syndrome o Common in interstitial nephritis
• Heavy metals: Cd, Pb, Hg → proximal tubular injury • Urine protein/creatinine ratio:
• Chemotherapy: Platinum drugs → hypomagnesemia, AKI o Normalizes for concentration/dilution
o Total protein:creatinine ratio ≠ albumin-specific
• Lithium: Nephrogenic DI, chronic interstitial nephritis o Light chains require urine protein electrophoresis for
• Aminoglycosides, Amphotericin-B: RTA, hearing loss detection
CHRONIC INTERSTITIAL NEPHRITIS Nephrotic Syndrome (NS)
• Causes: • Definition:
o Paraproteinemias (e.g., light chain nephropathy) o Proteinuria >3.5 g/day
o Analgesic nephropathy: o Hypoalbuminemia (<3.5 g/dL)
▪ NSAIDs, acetaminophen, phenacetin, caffeine o Edema
▪ May lead to urothelial cancers • Associated Features:
o Herbal nephropathy (aristolochic acid) o Hyperlipidemia (↑ LDL, ↓ HDL)
• Papillary necrosis: o Lipiduria:
o Phenacetin, DM, sickle-cell disease, analgesic use ▪ Oval fat bodies, Maltese crosses, fatty casts
o Loss of concentrating ability, sloughed papillae in urine o Edema:
• Nephrocalcinosis: ▪ Periorbital, facial, penile, scrotal
o Causes: hypercalcemia, hyperoxaluria, distal RTA, medullary ▪ Severe edema → bullae, ulceration, cellulitis
sponge kidney ▪ Vocal cord edema → hoarseness
o May be associated with nephrolithiasis • Atypical NS:
• Intestinal hyperoxaluria: o HIVAN: heavy proteinuria without edema
o Seen post-bowel surgery (e.g., Roux-en-Y), IBD o Collapsing glomerulopathy: rapid renal loss, common in
o Diagnosis: 24-h urine oxalate blacks with HIV
• Secondary FSGS causes:
INFECTIOUS TIN o Partial nephrectomy
• Acute pyelonephritis: o Chronic hypoxemia (lung/heart disease)
o AKI if bilateral or in solitary kidney o Obesity
• Chronic pyelonephritis: o Sickle cell disease
o Rarely causes chronic renal failure o Vasculitis
PROTEINURIC STATES AND NEPHROTIC SYNDROME o Urogenital anomalies
Proteinuric States • Metabolic state:
• Proteinuria can present with: o NS = hypercatabolic state
, o Albumin degradation > hepatic synthesis 1. Prerenal:
o Muehrcke’s lines: white lines in nail beds from o ↓ Renal perfusion (dehydration, low BP)
hypoalbuminemia o Low urinary Na+ (<20 mEq/L)
• Minimal Change Disease (MCD): o High urine osmolality, concentrated urine
o Common in children <6 years o Examples:
o Abrupt NS with high cholesterol ▪ Hypovolemia, NSAIDs, vasoconstrictors, contrast
o Secondary causes: Hodgkin’s lymphoma, allergies, ▪ Scleroderma, thrombotic microangiopathy
immunization ▪ Hypoxemia, cocaine
o May present with AKI in adults 2. Intrinsic Renal (Renal):
• Hereditary NS: o Damage to glomeruli, tubules, or interstitium
o Podocyte gene mutations (nephrin - NPHS1, podocin - o Urine Na+ >40 mEq/L, dilute urine
NPHS2) o Polyuria or oliguria, tubular dysfunction
• MN (Membranous Nephropathy): o Common cause: ATN
o Common in adults ▪ Ischemia, sepsis, toxins (drugs, myoglobin,
o Primary or secondary (e.g., drugs, infections, SLE, hemoglobin)
malignancies) ▪ Causes: NSAIDs, aminoglycosides, cisplatin,
o Associated with renal vein thrombosis (RVT): heroin, methotrexate
▪ Due to urinary loss of antithrombin-3, 3. Postrenal:
plasminogen, hyperfibrinogenemia o Obstruction (anuria if complete, polyuria if incomplete)
o Secondary MN causes: o Causes: BPH, stones, tumors
▪ NSAIDs, mercury, penicillamine, gold o Hydronephrosis on US
▪ Hepatitis B, syphilis, malaria, schistosomiasis o Exceptions:
▪ Solid tumors (lung, gastric, breast, etc.) ▪ Retroperitoneal fibrosis
▪ Anti-PLA2R antibodies (primary MN) ▪ Early obstruction (<4 days)
• MPGN / C3 glomerulopathy:
▪ Simultaneous volume depletion
o Nephrotic + nephritic features
CHRONIC KIDNEY DISEASE (CKD) AND UREMIC SYNDROME
o Low complement (C3)
CKD Characteristics
• Amyloidosis:
o May cause nephrogenic DI and hyperkalemic RTA • Progressive over months to years
o May present with Fanconi syndrome • Diagnosed by:
• Fanconi syndrome:
o eGFR <60 for ≥3 months
o Glycosuria, phosphaturia, uricosuria, aminoaciduria o Small kidneys (<8 cm) on US (except in diabetes or
amyloid—may be enlarged)
o Seen in multiple myeloma
o Cortical thinning
HEMATURIA AND LOWER URINARY TRACT SYNDROMES • Major causes:
o DM (~50% of ESRD)
• Source determination critical:
o Flank pain + colic → likely stone/obstruction o Hypertension, ischemic nephropathy, IgA nephropathy
o Flank pain w/o colic → infection, nephritis, obstruction, GN o Fibromuscular dysplasia (non-progressive)
o Gross hematuria + clots → lower tract (e.g., bladder) o PAN, Kawasaki disease (esp. post-COVID)
• Dangerous mimics: • Hereditary causes:
o Pain + HTN: may mimic stone but could be renal artery o ADPKD:
occlusion ▪ Bilateral cysts, liver cysts, possible cerebral
o Exercise-induced hematuria: resolves with rest aneurysm (circle of Willis)
o Hematuria vs. hemoglobinuria vs. myoglobinuria: o Alport syndrome:
▪ Distinguishable on urinalysis ▪ X-linked, COL4A5 mutation
▪ Hematuria, hearing loss, ocular defects
• Lower urinary symptoms: o Thin basement membrane disease:
o Dysuria, frequency, urgency, poor stream
o Causes: UTI, BPH ▪ Mild, familial hematuria
• Chronic hematuria: • Congenital abnormalities:
o Glomerular: thin basement membrane disease, hereditary o Horseshoe kidney, ectopic kidney
nephritis, IgA nephropathy
o Vesicoureteral reflux (childhood HTN, FSGS)
CKD Staging
• Evaluation:
o Persistent hematuria in age >40 warrants urologic and • Based on eGFR (MDRD, CKD-EPI, or cystatin-C)
cystoscopic exam • Race correction no longer preferred
o Review past records for chronicity Complications
• Fatigue, anorexia, weight loss, cognitive decline
ACUTE KIDNEY INJURY (AKI) • Neuropathy, restless legs, myoclonus
Definition • Nocturia → then oliguria
• Retention of nitrogenous wastes (↑BUN, creatinine) • Pruritus, GI bleeding, pericarditis
• BUN/Creatinine ratio increases with: • Anemia:
o Water reabsorption (high ADH) o From ↓EPO, iron deficiency
o Enhanced urea reabsorption o Target Hb: 10–12 g/dL
Categories • Electrolyte abnormalities:
, o Hyperkalemia, metabolic acidosis
o Secondary hyperparathyroidism (↓ calcitriol)
• Uremic syndrome:
o Encephalopathy, myoclonus, bleeding, pericarditis
• Tubular disorders:
o Fanconi syndrome: Proximal RTA, glycosuria,
aminoaciduria
o Bartter syndrome: Loop defect → hypokalemia,
hypercalciuria
o Gitelman syndrome: DCT defect → hypokalemia,
hypocalciuria
• Collecting duct defects:
o Nephrogenic DI
o Type 4 RTA (e.g., DM, amyloid, Addison's)
o Hypokalemia, alkalosis (e.g., Conn's syndrome, licorice)
RENAL MASSES AND BIOPSY INDICATIONS
• Renal cell carcinoma:
o May be incidental or present with flank mass, back pain,
hematuria
o May metastasize to bone, lung, marrow
• Other masses:
o Simple cysts, PKD, angiomyolipomas (tuberous sclerosis)
o Obstructive uropathy (pelviectasis)
• Imaging:
o Ultrasound: size, symmetry, obstruction, cysts
o Non-contrast CT: nephrolithiasis
o MRI: renal masses
o Avoid gadolinium in renal failure
o Nuclear scan: split renal function
• Biopsy:
o Needed for definitive diagnosis of many glomerular diseases
o Especially when cause unclear or diagnosis alters
management
URINARY TRACT DISEASE • Definition: Inflammatory kidney disease
• Causes:
o Infections, drug reactions, autoimmune disease, toxins
OVERVIEW OF URINARY TRACT STRUCTURE • Features:
• Upper urinary tract: o Enlarged tender kidneys
o Kidneys, renal vasculature, renal parenchyma, and collecting o Flank/CVA tenderness
system • Classification:
• Lower urinary tract: o Anatomical: vascular, glomerular, tubulointerstitial
o Ureters, bladder, urethra o Temporal: acute, subacute, chronic
• Urine production:
o Begins as plasma ultrafiltrate in glomeruli → modified by GLOMERULONEPHRITIS (GN)
renal tubules → excretion via urethra • Symptoms:
o Hypertension, edema, oliguria/anuria
PRESENTATION OF RENAL AND URINARY TRACT DISEASE o Dyspnea, orthopnea, ascites (esp. in children)
• Disease can be: • Urinalysis:
o Asymptomatic (e.g., incidental renal mass, microhematuria) o Hematuria (microscopic or gross), proteinuria
o Nonspecific (e.g., fatigue) o Dysmorphic RBCs, PMNs, RBC casts
o Syndrome-specific (e.g., proteinuria, nephritic syndrome) • Disease timeline:
o Pathognomonic (e.g., polycystic kidney disease) o Acute: postinfectious GN, RPGN
• Discovered via: o Chronic: years of progressive damage
o Lab testing
o Imaging (incidental findings) POSTINFECTIOUS GLOMERULONEPHRITIS (PIGN)
• Evaluate renal function when: • Etiology: Group A Streptococcus (pharyngitis, impetigo)
o Systemic disease is present (e.g., diabetes mellitus → • Timing: 10 days–3 weeks post-infection
screen for albuminuria) • Pathogenesis: Complement-mediated immune complex GN
o Known risk factors (e.g., lithium, lead, aniline dyes) • Labs: Low serum C3
• Clinical clues: Previous sore throat or skin infection
DIAGNOSTIC APPROACH TO RENAL DISEASE
• Differentials:
• Avoid premature random testing o Infection-related GN: e.g., MRSA abscess; ongoing infection
• Use structured approach: o IgA nephropathy (synpharyngitic hematuria):
o History: family history, toxins, birth weight, medication use ▪ Gross hematuria concurrent with infection
o Physical examination ▪ Normal C3
o Basic labs: urinalysis, blood chemistries
▪ Associations: celiac disease, RA, reactive arthritis,
• Determine: ankylosing spondylitis
o Region involved (glomeruli vs tubules) ▪ More common in Asians
o Time course (acute vs chronic)
• Glomerular dysfunction → hallmark: albuminuria RAPIDLY PROGRESSIVE GN (RPGN)
• Tubular dysfunction → electrolyte disturbances, issues with • Definition: Crescentic GN with rapid GFR decline
dilution/concentration • Histology: Crescents (proliferation of parietal epithelial cells,
• Chronicity causes overlap: inflammatory cells)
o Glomerular → tubular-interstitial scarring • Diffuse involvement: >50% glomeruli → high risk of sclerosis
o Tubular → secondary glomerular damage
• Clinical:
CASE EXAMPLE: CYSTINOSIS (Fanconi’s Syndrome in Children)
o Hemoptysis, epistaxis, sinusitis (pulmonary-renal syndrome)
• Early signs: • Types:
o Salt-wasting, polyuria, dehydration, poor growth o Pauci-immune GN (ANCA-positive):
o Hypokalemia, RTA, glycosuria, phosphaturia → renal rickets ▪ c-ANCA: proteinase-3 (granulomatosis with
polyangiitis)
• Later progression: ▪ p-ANCA: MPO (microscopic polyangiitis)
o Albuminuria, decreased GFR, retained K+ and phosphate
o Anti-GBM disease:
o Metabolic acidosis due to ↓ NH4⁺ production
▪ Renal-limited or Goodpasture syndrome (renal +
o Hypertension and edema
lung hemorrhage)
o Anemia (↓ erythropoietin)
o Nonspecific symptoms: weakness, fatigue, acidosis, carnitine ▪ Young males, smokers
deficiency o Immune complex RPGN:
▪ Low C3: lupus, cryoglobulinemia
• Specific finding:
o Photosensitivity from corneal cystine crystals ▪ Cryoglobulinemia: high RF, low C4, hepatitis C or
myeloma
• Differentials: ▪ IgA vasculitis (Henoch-Schönlein purpura):
o Hepatomegaly may suggest glycogen storage disease purpura, GI bleed, arthralgia, pulmonary
hemorrhage
MAJOR CLINICAL SYNDROMES IN RENAL DISEASE
▪ C3 deposits on biopsy but normal serum C3
,TUBULOINTERSTITIAL NEPHRITIS (TIN) o Generalized edema
o Foamy urine
ACUTE INTERSTITIAL NEPHRITIS (AIN) • Proteinuria ≠ Nephrotic Syndrome (NS)
• Causes: Drugs (most common), infection, autoimmunity • Microalbuminuria (MALB):
• Timing: 1 day–2 weeks post-drug exposure o First sign of glomerular damage in diabetes mellitus (DM)
• Drugs: o Defined as 30–300 mg/day of albumin excretion
o NSAIDs, beta-lactams, PPIs, sulfa drugs (e.g., o Detected by radioimmunoassay (not dipstick)
sulfamethoxazole), rifampin o Predicts progression to NS and renal failure
o CPIs (immune checkpoint inhibitors) o Associated with:
• Symptoms: ▪ Retinopathy (shared microvascular pathology)
o Fever, rash, eosinophilia ▪ Hypertension, obesity, poor glucose control
o Polyuria, nephrogenic diabetes insipidus, electrolyte ▪ Nephrectomy, hepatitis C
abnormalities ▪ APOL1 gene mutations (especially in African
• Urinalysis: ancestry, e.g., FSGS)
o Pyuria, eosinophiluria, WBC casts • Subnephrotic albuminuria:
o Activated T-cells, plasma cells on Giemsa stain o Focal glomerular diseases (<50% glomeruli involvement)
• Nephrotic proteinuria:
GRANULOMATOUS INTERSTITIAL NEPHRITIS o Involves most glomeruli (diffuse involvement)
• Drugs: Rifampin, CPIs • Dipstick proteinuria:
• Infections: TB (caseating granulomas), sarcoidosis (noncaseating) o Detects acidic proteins (like albumin)
• Location: Begins near glomeruli in TB o Cannot detect kappa/lambda light chains (multiple myeloma)
o Detectable albumin on dipstick = overt proteinuria
SYSTEMIC AND AUTOIMMUNE TIN • Overflow proteinuria:
• Diseases: o Due to low molecular weight proteins (e.g., light chains)
o SLE, Sjögren’s syndrome, ANCA vasculitis o Cross glomerular barrier freely
o TINU (Tubulointerstitial nephritis + uveitis) o Can damage glomeruli (e.g., AL amyloidosis, light-chain
nephropathy)
NONINFLAMMATORY INTERSTITIAL NEPHROPATHY • Tubular proteinuria:
o Caused by proximal tubular dysfunction
TOXIN-RELATED o β-2 microglobulin is the main protein
• Ifosfamide: Fanconi syndrome o Common in interstitial nephritis
• Heavy metals: Cd, Pb, Hg → proximal tubular injury • Urine protein/creatinine ratio:
• Chemotherapy: Platinum drugs → hypomagnesemia, AKI o Normalizes for concentration/dilution
o Total protein:creatinine ratio ≠ albumin-specific
• Lithium: Nephrogenic DI, chronic interstitial nephritis o Light chains require urine protein electrophoresis for
• Aminoglycosides, Amphotericin-B: RTA, hearing loss detection
CHRONIC INTERSTITIAL NEPHRITIS Nephrotic Syndrome (NS)
• Causes: • Definition:
o Paraproteinemias (e.g., light chain nephropathy) o Proteinuria >3.5 g/day
o Analgesic nephropathy: o Hypoalbuminemia (<3.5 g/dL)
▪ NSAIDs, acetaminophen, phenacetin, caffeine o Edema
▪ May lead to urothelial cancers • Associated Features:
o Herbal nephropathy (aristolochic acid) o Hyperlipidemia (↑ LDL, ↓ HDL)
• Papillary necrosis: o Lipiduria:
o Phenacetin, DM, sickle-cell disease, analgesic use ▪ Oval fat bodies, Maltese crosses, fatty casts
o Loss of concentrating ability, sloughed papillae in urine o Edema:
• Nephrocalcinosis: ▪ Periorbital, facial, penile, scrotal
o Causes: hypercalcemia, hyperoxaluria, distal RTA, medullary ▪ Severe edema → bullae, ulceration, cellulitis
sponge kidney ▪ Vocal cord edema → hoarseness
o May be associated with nephrolithiasis • Atypical NS:
• Intestinal hyperoxaluria: o HIVAN: heavy proteinuria without edema
o Seen post-bowel surgery (e.g., Roux-en-Y), IBD o Collapsing glomerulopathy: rapid renal loss, common in
o Diagnosis: 24-h urine oxalate blacks with HIV
• Secondary FSGS causes:
INFECTIOUS TIN o Partial nephrectomy
• Acute pyelonephritis: o Chronic hypoxemia (lung/heart disease)
o AKI if bilateral or in solitary kidney o Obesity
• Chronic pyelonephritis: o Sickle cell disease
o Rarely causes chronic renal failure o Vasculitis
PROTEINURIC STATES AND NEPHROTIC SYNDROME o Urogenital anomalies
Proteinuric States • Metabolic state:
• Proteinuria can present with: o NS = hypercatabolic state
, o Albumin degradation > hepatic synthesis 1. Prerenal:
o Muehrcke’s lines: white lines in nail beds from o ↓ Renal perfusion (dehydration, low BP)
hypoalbuminemia o Low urinary Na+ (<20 mEq/L)
• Minimal Change Disease (MCD): o High urine osmolality, concentrated urine
o Common in children <6 years o Examples:
o Abrupt NS with high cholesterol ▪ Hypovolemia, NSAIDs, vasoconstrictors, contrast
o Secondary causes: Hodgkin’s lymphoma, allergies, ▪ Scleroderma, thrombotic microangiopathy
immunization ▪ Hypoxemia, cocaine
o May present with AKI in adults 2. Intrinsic Renal (Renal):
• Hereditary NS: o Damage to glomeruli, tubules, or interstitium
o Podocyte gene mutations (nephrin - NPHS1, podocin - o Urine Na+ >40 mEq/L, dilute urine
NPHS2) o Polyuria or oliguria, tubular dysfunction
• MN (Membranous Nephropathy): o Common cause: ATN
o Common in adults ▪ Ischemia, sepsis, toxins (drugs, myoglobin,
o Primary or secondary (e.g., drugs, infections, SLE, hemoglobin)
malignancies) ▪ Causes: NSAIDs, aminoglycosides, cisplatin,
o Associated with renal vein thrombosis (RVT): heroin, methotrexate
▪ Due to urinary loss of antithrombin-3, 3. Postrenal:
plasminogen, hyperfibrinogenemia o Obstruction (anuria if complete, polyuria if incomplete)
o Secondary MN causes: o Causes: BPH, stones, tumors
▪ NSAIDs, mercury, penicillamine, gold o Hydronephrosis on US
▪ Hepatitis B, syphilis, malaria, schistosomiasis o Exceptions:
▪ Solid tumors (lung, gastric, breast, etc.) ▪ Retroperitoneal fibrosis
▪ Anti-PLA2R antibodies (primary MN) ▪ Early obstruction (<4 days)
• MPGN / C3 glomerulopathy:
▪ Simultaneous volume depletion
o Nephrotic + nephritic features
CHRONIC KIDNEY DISEASE (CKD) AND UREMIC SYNDROME
o Low complement (C3)
CKD Characteristics
• Amyloidosis:
o May cause nephrogenic DI and hyperkalemic RTA • Progressive over months to years
o May present with Fanconi syndrome • Diagnosed by:
• Fanconi syndrome:
o eGFR <60 for ≥3 months
o Glycosuria, phosphaturia, uricosuria, aminoaciduria o Small kidneys (<8 cm) on US (except in diabetes or
amyloid—may be enlarged)
o Seen in multiple myeloma
o Cortical thinning
HEMATURIA AND LOWER URINARY TRACT SYNDROMES • Major causes:
o DM (~50% of ESRD)
• Source determination critical:
o Flank pain + colic → likely stone/obstruction o Hypertension, ischemic nephropathy, IgA nephropathy
o Flank pain w/o colic → infection, nephritis, obstruction, GN o Fibromuscular dysplasia (non-progressive)
o Gross hematuria + clots → lower tract (e.g., bladder) o PAN, Kawasaki disease (esp. post-COVID)
• Dangerous mimics: • Hereditary causes:
o Pain + HTN: may mimic stone but could be renal artery o ADPKD:
occlusion ▪ Bilateral cysts, liver cysts, possible cerebral
o Exercise-induced hematuria: resolves with rest aneurysm (circle of Willis)
o Hematuria vs. hemoglobinuria vs. myoglobinuria: o Alport syndrome:
▪ Distinguishable on urinalysis ▪ X-linked, COL4A5 mutation
▪ Hematuria, hearing loss, ocular defects
• Lower urinary symptoms: o Thin basement membrane disease:
o Dysuria, frequency, urgency, poor stream
o Causes: UTI, BPH ▪ Mild, familial hematuria
• Chronic hematuria: • Congenital abnormalities:
o Glomerular: thin basement membrane disease, hereditary o Horseshoe kidney, ectopic kidney
nephritis, IgA nephropathy
o Vesicoureteral reflux (childhood HTN, FSGS)
CKD Staging
• Evaluation:
o Persistent hematuria in age >40 warrants urologic and • Based on eGFR (MDRD, CKD-EPI, or cystatin-C)
cystoscopic exam • Race correction no longer preferred
o Review past records for chronicity Complications
• Fatigue, anorexia, weight loss, cognitive decline
ACUTE KIDNEY INJURY (AKI) • Neuropathy, restless legs, myoclonus
Definition • Nocturia → then oliguria
• Retention of nitrogenous wastes (↑BUN, creatinine) • Pruritus, GI bleeding, pericarditis
• BUN/Creatinine ratio increases with: • Anemia:
o Water reabsorption (high ADH) o From ↓EPO, iron deficiency
o Enhanced urea reabsorption o Target Hb: 10–12 g/dL
Categories • Electrolyte abnormalities:
, o Hyperkalemia, metabolic acidosis
o Secondary hyperparathyroidism (↓ calcitriol)
• Uremic syndrome:
o Encephalopathy, myoclonus, bleeding, pericarditis
• Tubular disorders:
o Fanconi syndrome: Proximal RTA, glycosuria,
aminoaciduria
o Bartter syndrome: Loop defect → hypokalemia,
hypercalciuria
o Gitelman syndrome: DCT defect → hypokalemia,
hypocalciuria
• Collecting duct defects:
o Nephrogenic DI
o Type 4 RTA (e.g., DM, amyloid, Addison's)
o Hypokalemia, alkalosis (e.g., Conn's syndrome, licorice)
RENAL MASSES AND BIOPSY INDICATIONS
• Renal cell carcinoma:
o May be incidental or present with flank mass, back pain,
hematuria
o May metastasize to bone, lung, marrow
• Other masses:
o Simple cysts, PKD, angiomyolipomas (tuberous sclerosis)
o Obstructive uropathy (pelviectasis)
• Imaging:
o Ultrasound: size, symmetry, obstruction, cysts
o Non-contrast CT: nephrolithiasis
o MRI: renal masses
o Avoid gadolinium in renal failure
o Nuclear scan: split renal function
• Biopsy:
o Needed for definitive diagnosis of many glomerular diseases
o Especially when cause unclear or diagnosis alters
management
