Major Nonglomerular Disorders

Tejas Desai, MD, Assistant Professor of Medicine

Major Nonglomerular Disorders

Urinary Tract Obstruction Tubulo-interstitial Nephropathy Cystic Diseases of the Kidney Nephrolithiasis Renal Tumors

Case #1 82 yo man with long hx urinary hesitancy

presents to the ED with c/o decreased urine output; he is otherwise without symptoms

Na+ 132 K+ 6.6 Cl- 102 HCO3- 12

BUN 38 creat 4.4 Renal U/S with bilat hydronephrosis Foley catheter placed with 1.2 l U/O before

clamped 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

TURP scheduled by urology in 3 weeks

Urinary Tract Obstruction 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

Change in urinary habits is often the presenting problem…..urinary hesitancy, nocturia, incontinence

must be R/O in any pt who presents with unexplained renal insufficiency

renal U/S will show hydronephrosis 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

Causes of Urinary Tract Obstruction

Congenital urinary tract malformation : posterior urethral valves, meatal stenosis, etc

intraluminal obstruction : stones, clots, sloughed papillae

extrinsic compression : prostatic hypertrophy, pelvic tumors, retroperitoneal fibrosis

acquired anomalies : urethral stricture, neurogenic bladder

Case #1½ 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

BP 122/68 HR 82 afeb Exam very benign w/ clear lungs, nl heart sounds, & only minor LE edema

Na+ 144 K+ 6.1 Cl- 100 HCO3- 16

BUN 16 creat 1.8 What is the cause of the acidosis,

hyperkalemia and CRF ? Is it one process ?

Tubulo-interstitial Nephropathy (TIN)

Clinical disorders that affect renal tubules and interstitium principally with sparing of glomeruli and renal vasculature

Acute interstitial nephritis (AIN) causes rapid decline in renal function (days to weeks); characterized histologically by an acute inflammatory infiltrate

Chronic interstitial nephropathy (CIN) causes slowly progressive (years) renal insufficiency characterized by interstitial scarring/fibrosis with less active inflammation

Diagnosis and Clinical Features of CIN

CIN is characterized by tubular defects that are prominent and disproportionate to degree of azotemia (ie, bad tubular defects with only modest GFR)

Usually little or no clinical evidence of active inflammation (scar & fibrosis); UA often bland, ie, mild pyuria, minimal hematuria, no cellular casts

Many diseases affect specific segments of the tubule altering those tubular functions most prominently

Diagnosis and Clinical Features of CIN Primarily proximal tubule injury may present

with proximal RTA (RTA, type II), glycosuria, amino aciduria & uricosuria ~ seen in multiple myeloma or heavy metal toxicity

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

urinary concentrating defects may occur with medullary involvement as in analgesic nephropathy, sickle cell nephropathy or polycystic kidney disease

Conditions Associated with CIN Urinary tract obstruction, reflux nephropathy Drugs : analgesics/NSAIDs, nitrosurea,cisplatin,

cyclosporine, lithium Heavy Metals : lead, cadmium Malignancies & granulomatous diseases : multiple

myeloma, sarcoidosis, tuberculosis,Wegener’s granulomatosis

Immunologic diseases: SLE, Sjogren’s syndrome, cryoglobulinemia, amyloidosis, vasculitis

Hereditary diseases : Medullary cystic disease, hereditary nephritis, Polycystic Kidney Disease, sickle cell nephropathy

Metabolic disorders : Hyperuricemia, hypercalcemia, hyperoxaluria (oxalosis), cystinosis

Other : Radiation nephritis, Balkan nephropathy

Case #2 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

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

Na+ 140 K+ 4.2 Cl- 100 HCO3- 22

BUN 18 creat 1.6 Ccreat 105ml/min Hgb 16 gm/dl Abd U/S shows large kidneys bilaterally with

multiple cysts and a few hepatic cysts

Cystic Disease of the Kidney

Renal cysts are characterized by epithelium lined cavities filled with fluid

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

complex cysts are cavities with septae or debris which can represent hemorrhage or infection BUT malignancy must be ruled out

Polycystic Kidney Disease (PKD)

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

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

Complete penetrance of the gene is expected to occur by age 90

Clinical Manifestations of PKD 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

may be diagnosed on screening done based on +FMH (ie, pt has no sx) or due to hematuria

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

HTN occurs in ~60% of PKD pts before onset of renal insufficiency

Clinical Manifestations of PKD Nocturia due to renal concentrating defect &

impaired salt conservation even on Na+ restricted diet (ie, salt wasting nephropathy)

UTI & pyelonephritis are common complications (and dreaded due to risk for cyst infection)

up to 10% of PKD pts have multiple, asymptomatic hepatic cysts rare progression to liver failure

10% of PKD pts have cerebral aneurysms (+FMH extremely important)

25% of PKD pts have mitral valve prolapse polycythemia due to EPO production by cysts 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

Diagnosis of PKD Imaging studies showing multiple cysts

distributed throughout the renal parenchyma bilaterally, enlarged kidneys, elongation/splaying of renal calyces ~ usually found on U/S

Stones more frequent due to ↓ urinary citrate extra renal involvement, esp. presence of

hepatic cysts, lends support to dx of PKD 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

Treatment of PKD

Prevent complications & preserve renal function

be aggressive in treatment of UTIs, vigilant in monitoring for stones & control HTN

Educate pt on hereditary nature of disease and its complications

dialysis/transplantation when ESRD occurs; ? Nephrectomy prior to transplant if lots of cyst infections/hemorrhage or inordinately large kidneys (mechanical issue)

Acquired Cystic Disease

Refers to multiple small cysts which develop over time in ESRD pts on dialysis

CT better than U/S to define due to small scarred kidneys & small cysts

major concern is increased risk for development of renal cell carcinoma

pt needs W/U if marked increase in Hgb occurs (without change in EPO dosing), flank pain, hematuria

Medullary Cystic Disorders

Medullary cystic disease is rare, autosomal recessive disease sometimes associated with retinitis pigmentosa

prolonged enuresis in childhood due to concentrating defects as well as anemia are indicators of disease

neither radiologic imaging or renal biopsy has good yield in demonstrating small medullary cysts

often culminates in ESRD during adolescence or early adulthood

Medullary Cystic Disorders Medullary Sponge Kidney is a more common &

more benign disorder often detected incidentally on abdominal X-rays

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

best diagnosed w/ IVP where medullary cysts are outlined by contrast & appear as characteristic radial pattern (“bouquet of flowers”)

treatment aimed at UTI, stone formation; progression to ESRD does not occur due to basic disease (but can occur due to its complications)

Case #2½ 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

BP 194/110 HR 108 afeb Exam: benign; abd still with large palpable kidneys but no tenderness to palpation

Na+ 139 K+ 4.4 Cl- 99 HCO3- 23

BUN 28 creat 1.6 WBC 6.8 Hgb 16.3 plt 300K

Renal U/S: large cystic kidneys, bilat calyceal stones, mild hydronephrosis on right w/ureteral calculus

Nephrolithiasis 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

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%

pts usually present w/ hematuria (gross or micro) and acute excruciating colicky pain located in the flank w/ radiation to the groin

Eval should include detailed history (esp. previous episodes of stones, UTIs, hematuria), FMH, dietary history, drug history

Nephrolithiasis

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

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)

stones which are obstructing and do not pass spontaneously will require surgical removal (either by lithotripsy or cystoscopically)

Case #3 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

BP 132/82 HR 88 afeb Exam: lungs clear, heart sounds nl, abd distended with dialysate but no tenderness, tr LE edema

Na+ 136 K+ 3.6 Cl- 99 HCO3- 22

BUN 65 creat 7.0 Hgb 14.2 (Epo D/C last month)

Renal CT scan shows small cysts scattered throughout small kidneys; in left kidney there is a larger complex cyst

Renal Tumors Most renal tumors seem to arise from the

tubulointerstitial compartment of the kidney; renal cell carcinoma is felt to be of proximal tubule origin

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

Renal cell carcinoma (hypernephroma) is the most frequent malignant renal neoplasm in adults and accounts for ~2% of cancer deaths

Renal Tumors 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

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)

3 cell types : clear cells, granular cells and spindle cells

Renal Tumors RCC is highly vascular, supplied by vessels w/thin,

amuscular walls; extension of the tumor into normal renal veins/IVC is not uncommon

Metastasis is chiefly by hematogenous spread to lungs, bone and liver

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

Treatment is surgical; response is poor to chemo and radiation therapies

survival is related to cell type, local extension, & distant metastasis; ranges from 10-50 % for 10 yr survival