Major Nonglomerular Disorders


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Major Nonglomerular Disorders

  1. 1. Major Nonglomerular Disorders Tejas Desai, MD, Assistant Professor of Medicine
  2. 2. Major Nonglomerular Disorders <ul><li>Urinary Tract Obstruction </li></ul><ul><li>Tubulo-interstitial Nephropathy </li></ul><ul><li>Cystic Diseases of the Kidney </li></ul><ul><li>Nephrolithiasis </li></ul><ul><li>Renal Tumors </li></ul>
  3. 3. Case #1 <ul><li>82 yo man with long hx urinary hesitancy presents to the ED with c/o decreased urine output; he is otherwise without symptoms </li></ul><ul><li>Na + 132 K + 6.6 Cl - 102 HCO 3 - 12 </li></ul><ul><li>BUN 38 creat 4.4 </li></ul><ul><li>Renal U/S with bilat hydronephrosis </li></ul><ul><li>Foley catheter placed with 1.2 l U/O before clamped </li></ul><ul><li>Admitted for observation; creat ↓ 1.8, K + ↓ 5.4, U/O 3.1 l/day with urine osmo 260 at time of D/C 5 days later with indwelling Foley catheter </li></ul><ul><li>TURP scheduled by urology in 3 weeks </li></ul>
  4. 5. Urinary Tract Obstruction <ul><li>Obstruction can occur at any point from the renal pelvis to the urethral meatus BUT must be bilateral to cause renal failure; unilateral renal obstruction can be asymptomatic </li></ul><ul><li>Change in urinary habits is often the presenting problem…..urinary hesitancy, nocturia, incontinence </li></ul><ul><li>must be R/O in any pt who presents with unexplained renal insufficiency </li></ul><ul><li>renal U/S will show hydronephrosis </li></ul><ul><li>management is aimed at relieving the obstruction; need to anticipate a post obstructive diuresis (due to osmotic diuresis & concentrating defect) and replace fluids & monitor electrolytes </li></ul>
  5. 6. Causes of Urinary Tract Obstruction <ul><li>Congenital urinary tract malformation : posterior urethral valves, meatal stenosis, etc </li></ul><ul><li>intraluminal obstruction : stones, clots, sloughed papillae </li></ul><ul><li>extrinsic compression : prostatic hypertrophy, pelvic tumors, retroperitoneal fibrosis </li></ul><ul><li>acquired anomalies : urethral stricture, neurogenic bladder </li></ul>
  6. 7. Case #1½ <ul><li>Same elderly gentleman comes back to your office for F/U 2 months after uneventful TURP with no c/o voiding difficulty, volume overload sx or uremic sx </li></ul><ul><li>BP 122/68 HR 82 afeb Exam very benign w/ clear lungs, nl heart sounds, & only minor LE edema </li></ul><ul><li>Na + 144 K + 6.1 Cl - 100 HCO 3 - 16 BUN 16 creat 1.8 </li></ul><ul><li>What is the cause of the acidosis, hyperkalemia and CRF ? Is it one process ? </li></ul>
  7. 8. Tubulo-interstitial Nephropathy (TIN) <ul><li>Clinical disorders that affect renal tubules and interstitium principally with sparing of glomeruli and renal vasculature </li></ul><ul><li>Acute interstitial nephritis (AIN) causes rapid decline in renal function (days to weeks); characterized histologically by an acute inflammatory infiltrate </li></ul><ul><li>Chronic interstitial nephropathy (CIN) causes slowly progressive (years) renal insufficiency characterized by interstitial scarring/fibrosis with less active inflammation </li></ul>
  8. 9. Diagnosis and Clinical Features of CIN <ul><li>CIN is characterized by tubular defects that are prominent and disproportionate to degree of azotemia (ie, bad tubular defects with only modest  GFR) </li></ul><ul><li>Usually little or no clinical evidence of active inflammation (scar & fibrosis); UA often bland, ie, mild pyuria, minimal hematuria, no cellular casts </li></ul><ul><li>Many diseases affect specific segments of the tubule  altering those tubular functions most prominently </li></ul>
  9. 10. Diagnosis and Clinical Features of CIN <ul><li>Primarily proximal tubule injury may present with proximal RTA (RTA, type II), glycosuria, amino aciduria & uricosuria ~ seen in multiple myeloma or heavy metal toxicity </li></ul><ul><li>distal RTA (RTA, type I,IV), salt wasting & hypo or hyperkalemia may be seen with primarily distal tubule injury as seen with chronic obstruction or amyloidosis </li></ul><ul><li>urinary concentrating defects may occur with medullary involvement as in analgesic nephropathy, sickle cell nephropathy or polycystic kidney disease </li></ul>
  10. 11. Conditions Associated with CIN <ul><li>Urinary tract obstruction, reflux nephropathy </li></ul><ul><li>Drugs : analgesics/NSAIDs, nitrosurea,cisplatin, cyclosporine, lithium </li></ul><ul><li>Heavy Metals : lead, cadmium </li></ul><ul><li>Malignancies & granulomatous diseases : multiple myeloma, sarcoidosis, tuberculosis,Wegener’s granulomatosis </li></ul><ul><li>Immunologic diseases: SLE, Sjogren’s syndrome, cryoglobulinemia, amyloidosis, vasculitis </li></ul><ul><li>Hereditary diseases : Medullary cystic disease, hereditary nephritis, Polycystic Kidney Disease, sickle cell nephropathy </li></ul><ul><li>Metabolic disorders : Hyperuricemia, hypercalcemia, hyperoxaluria (oxalosis), cystinosis </li></ul><ul><li>Other : Radiation nephritis, Balkan nephropathy </li></ul>
  11. 12. Case #2 <ul><li>40 yo man presents to your office with c/o gross hematuria x 3 weeks; he has been ‘healthy’ his whole life and last saw a doctor when he was in the service 20yrs ago; currently asymptomatic with no fever, dysuria or pain; he is worried because his older brother and father are known to have ADPKD but he says an U/S done at the military hospital showed no cysts when he was 18 yo </li></ul><ul><li>BP 160/100 HR 72 afeb wgt 280 lbs ht 6’5” Exam: clear lungs, +S4 on cardiac exam, large palpable kidneys bilat, no edema </li></ul><ul><li>Na + 140 K + 4.2 Cl - 100 HCO 3 - 22 BUN 18 creat 1.6 Ccreat 105ml/min Hgb 16 gm/dl </li></ul><ul><li>Abd U/S shows large kidneys bilaterally with multiple cysts and a few hepatic cysts </li></ul>
  12. 14. Cystic Disease of the Kidney <ul><li>Renal cysts are characterized by epithelium lined cavities filled with fluid </li></ul><ul><li>simple cysts increase in frequency with age being present in up to 50% of the population over age 50; usually asymptomatic & found incidentally on an imaging study </li></ul><ul><li>complex cysts are cavities with septae or debris which can represent hemorrhage or infection BUT malignancy must be ruled out </li></ul>
  13. 16. Polycystic Kidney Disease (PKD) <ul><li>ADPKD (adults) and ARPKD (infantile) are the 2 main types of PKD; ARPKD occurs in association with congenital hepatic fibrosis & causes death from renal failure within the first year of life </li></ul><ul><li>ADPKD is the most common hereditary disease in the USA, affecting >500,000 people: the most common genotype (ADPKD 1) is located on chromosome 16 but other forms exist </li></ul><ul><li>Complete penetrance of the gene is expected to occur by age 90 </li></ul>
  14. 18. Clinical Manifestations of PKD <ul><li>Cysts rarely occur before age 20-25 yrs; ie, you can pass the gene to your offspring before you are even aware that you may have a genetically transmissible disease </li></ul><ul><li>may be diagnosed on screening done based on +FMH (ie, pt has no sx) or due to hematuria </li></ul><ul><li>flank pain & hematuria are the most common clinical manifestations; vague, dull lumbar pain may occur when kidneys are significantly enlarged; sharp localized pain may occur with cyst rupture or infection or passage of a stone </li></ul><ul><li>HTN occurs in ~60% of PKD pts before onset of renal insufficiency </li></ul>
  15. 19. Clinical Manifestations of PKD <ul><li>Nocturia due to renal concentrating defect & impaired salt conservation even on Na + restricted diet (ie, salt wasting nephropathy) </li></ul><ul><li>UTI & pyelonephritis are common complications (and dreaded due to risk for cyst infection) </li></ul><ul><li>up to 10% of PKD pts have multiple, asymptomatic hepatic cysts  rare progression to liver failure </li></ul><ul><li>10% of PKD pts have cerebral aneurysms (+FMH extremely important) </li></ul><ul><li>25% of PKD pts have mitral valve prolapse </li></ul><ul><li>polycythemia due to  EPO production by cysts </li></ul><ul><li>natural history of PKD variable  progresses to ESRD in ~25% of pts by age 50 & in ~50% by age 70; male > female in rates of progression </li></ul>
  16. 20. Diagnosis of PKD <ul><li>Imaging studies showing multiple cysts distributed throughout the renal parenchyma bilaterally, enlarged kidneys, elongation/splaying of renal calyces ~ usually found on U/S </li></ul><ul><li>Stones more frequent due to ↓ urinary citrate </li></ul><ul><li>extra renal involvement, esp. presence of hepatic cysts, lends support to dx of PKD </li></ul><ul><li>Identification of ADPKD 1 gene through gene linkage analysis ~ very expensive, requires family cooperation & provides no anatomic information; best reserved for pts with sx but nondiagnostic imaging </li></ul>
  17. 21. Treatment of PKD <ul><li>Prevent complications & preserve renal function </li></ul><ul><li>be aggressive in treatment of UTIs, vigilant in monitoring for stones & control HTN </li></ul><ul><li>Educate pt on hereditary nature of disease and its complications </li></ul><ul><li>dialysis/transplantation when ESRD occurs; ? Nephrectomy prior to transplant if lots of cyst infections/hemorrhage or inordinately large kidneys (mechanical issue) </li></ul>
  18. 22. Acquired Cystic Disease <ul><li>Refers to multiple small cysts which develop over time in ESRD pts on dialysis </li></ul><ul><li>CT better than U/S to define due to small scarred kidneys & small cysts </li></ul><ul><li>major concern is increased risk for development of renal cell carcinoma </li></ul><ul><li>pt needs W/U if marked increase in Hgb occurs (without change in EPO dosing), flank pain, hematuria </li></ul>
  19. 23. Medullary Cystic Disorders <ul><li>Medullary cystic disease is rare, autosomal recessive disease sometimes associated with retinitis pigmentosa </li></ul><ul><li>prolonged enuresis in childhood due to concentrating defects as well as anemia are indicators of disease </li></ul><ul><li>neither radiologic imaging or renal biopsy has good yield in demonstrating small medullary cysts </li></ul><ul><li>often culminates in ESRD during adolescence or early adulthood </li></ul>
  20. 24. Medullary Cystic Disorders <ul><li>Medullary Sponge Kidney is a more common & more benign disorder often detected incidentally on abdominal X-rays </li></ul><ul><li>often presents with stone passage; ~10% of pts presenting with renal stones will have medullary sponge kidney; nephrocalcinosis occurs in ~50% of pts which aids in detection on plain films </li></ul><ul><li>best diagnosed w/ IVP where medullary cysts are outlined by contrast & appear as characteristic radial pattern (“bouquet of flowers”) </li></ul><ul><li>treatment aimed at UTI, stone formation; progression to ESRD does not occur due to basic disease (but can occur due to its complications) </li></ul>
  21. 25. Case #2½ <ul><li>The same patient presents to your office 3 years later with c/o recurrent gross hematuria x 24hrs; this time however, he c/o severe right flank pain radiating to the groin which waxes and wanes in intensity but never goes away completely; he has no fever, chills or dysuria prior to this episode; +N/V </li></ul><ul><li>BP 194/110 HR 108 afeb Exam: benign; abd still with large palpable kidneys but no tenderness to palpation </li></ul><ul><li>Na + 139 K + 4.4 Cl - 99 HCO 3 - 23 BUN 28 creat 1.6 WBC 6.8 Hgb 16.3 plt 300K </li></ul><ul><li>Renal U/S: large cystic kidneys, bilat calyceal stones, mild hydronephrosis on right w/ureteral calculus </li></ul>
  22. 27. Nephrolithiasis <ul><li>Common ; peak incidence in pts age 18-45 yrs; 5-10x more common in males; high incidence in more affluent white males felt related to diet </li></ul><ul><li>4 types of renal calculi : calcium stones are most common accounting for ~75% of all stones; uric acid stones account for 10-15%; triple phosphate (struvite) stones 10-15%; cystine stones 1% </li></ul><ul><li>pts usually present w/ hematuria (gross or micro) and acute excruciating colicky pain located in the flank w/ radiation to the groin </li></ul><ul><li>Eval should include detailed history (esp. previous episodes of stones, UTIs, hematuria), FMH, dietary history, drug history </li></ul>
  23. 29. Nephrolithiasis <ul><li>40% of pts with a first episode of stones have a second episode within 2-3 yrs & 75% will have a recurrence in 10 yrs </li></ul><ul><li>every pt presenting with their first stone should be educated to increase their fluid intake to ~3l/ day and to decrease dietary protein intake to more modest levels (.8-1 gm/kg/day) </li></ul><ul><li>stones which are obstructing and do not pass spontaneously will require surgical removal (either by lithotripsy or cystoscopically) </li></ul>
  24. 30. Case #3 <ul><li>58 yo peritoneal dialysis patient comes into clinic for routine visit feeling well; on routine questioning, he reports gross hematuria intermittently x 3 weeks where previously he had made very little urine; this did not concern him because he also has a hx of stones </li></ul><ul><li>BP 132/82 HR 88 afeb Exam: lungs clear, heart sounds nl, abd distended with dialysate but no tenderness, tr LE edema </li></ul><ul><li>Na + 136 K + 3.6 Cl - 99 HCO 3 - 22 BUN 65 creat 7.0 Hgb 14.2 (Epo D/C last month) </li></ul><ul><li>Renal CT scan shows small cysts scattered throughout small kidneys; in left kidney there is a larger complex cyst </li></ul>
  25. 34. Renal Tumors <ul><li>Most renal tumors seem to arise from the tubulointerstitial compartment of the kidney; renal cell carcinoma is felt to be of proximal tubule origin </li></ul><ul><li>Renal cell carcinoma has been dubbed the “internist’s tumor” because it is suspected based on clinical presentation of the classic triad of hematuria, abdominal/flank mass and flank pain; unfortunately, the full triad is seen in only 10% of pts but at least one of these is present in well over 50% of pts </li></ul><ul><li>Renal cell carcinoma (hypernephroma) is the most frequent malignant renal neoplasm in adults and accounts for ~2% of cancer deaths </li></ul>
  26. 35. Renal Tumors <ul><li>Renal Cell Carcinoma is notable for large number of systemic, extrarenal manifestations : fever (~20%),  ESR (~50%), anemia (~30%), polycythemia in some cases, reversible hepatic dysfunction, peripheral neuropathy </li></ul><ul><li>Ectopic hormone syndromes associated w/RCC include hypercalcemia (from OAF) frequently associated with bone metastasis and Cushing’s syndrome (from tumor production of ACTH-like factor) </li></ul><ul><li>3 cell types : clear cells, granular cells and spindle cells </li></ul>
  27. 36. Renal Tumors <ul><li>RCC is highly vascular, supplied by vessels w/thin, amuscular walls; extension of the tumor into normal renal veins/IVC is not uncommon </li></ul><ul><li>Metastasis is chiefly by hematogenous spread to lungs, bone and liver </li></ul><ul><li>tumors often undergo cystic internal degeneration and can mimic simple cysts on U/S…..complex cysts should always seen as suspicious, esp. if internal calcifications are present </li></ul><ul><li>Treatment is surgical; response is poor to chemo and radiation therapies </li></ul><ul><li>survival is related to cell type, local extension, & distant metastasis; ranges from 10-50 % for 10 yr survival </li></ul>