AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY

ACQUIRED CYSTIC KIDNEY DISEASE IN RENAL FAILURE

JUVENILE NEPHRONOPHTHISIS–MEDULLARY CYSTIC KIDNEY DISEASE COMPLEX

Chinese Herb Nephropathy and Balkan Endemic Nephropathy

CRYSTAL DEPOSITION DISORDERS AND OBSTRuCTIVE TuBuLOPATHIES

Acute TIN: most often presents w/ ARF; aggressive inflammatory infiltrate--> tissue edema, tubular cell injury, and compromised tubular flow, OR frank obstruction of tubules w/ casts, cellular debris, or crystals; sometimes flank pain due to distention of renal capsule; Urinary sediment often active w/ leukocytes and cellular casts

clinical features: more indolent; may manifest w/ disorders of tubular function (polyuria from impaired concentrating ability (DI), defective PT reabsorption (features of Fanconi’s syndrome (glycosuria, phosphaturia, aminoaciduria, hypokalemia, and type II renal tubular acidosis [RTA] from bicarbonaturia)), or NAGMA and hyperkalemia (type IV RTA) due to impaired ammoniagenesis, as well as progressive azotemia (rising creatinine and BUN))
often modest proteinuria (rarely >2 g/d) attributable to decr tubular reabsorption of filtered prs; nephrotic-range albuminuria may occur in some conditions due to development of FSGS

sono: may reveal changes of “medical renal disease,” such as incr echogenicity of renal parenchyma w/ loss of corticomedullary differentiation, prominence of renal pyramids, and cortical scarring in some conditions.

predominant pathology in chronic TIN: interstitial fibrosis w/ patchy mononuclear cell infiltration and widespread tubular atrophy, luminal dilation, and thickening of tubular basement membranes.
nonspecific nature of histopathology--> biopsy specimens rarely provide a specific diagnosis--> diagnosis relies on careful analysis of Hx, drug or toxin exposure, associated symptoms, and imaging studies

Diagnosis: [Finding otherwise unexplained RF and exposure to a potentially offending agent usually points to diagnosis] Peripheral blood eosinophilia adds supporting evidence but present in only a minority of patients. biopsy not required

classic presentation: fever, rash, peripheral eosinophilia, and oliguric renal failure occurring after 7–10 days of treatment w/ methicillin or another β-lactam antibiotic: is the exception rather than the rule.

More often: found incidentally to have a rising serum creatinine or present w/ symptoms attributable to ARF.

Atypical reactions can occur, most notably NSAID-induced AIN, in which fever, rash, and eosinophilia are rare, but acute renal failure w/ heavy proteinuria common.

ASSOCIATED MEDICAL CONDITIONS: Nephrolithiasis is a systemic disorder.

conditions predisposing: GI malabsorption (Crohn’s disease, gastric bypass surgery), primary hyperPTH, obesity, DM II, and distal RTA
other medical conditions more likely to be present in individuals w/ hx of nephrolithiasis: HTN, gout, cholelithiasis, reduced bone mineral density, and CKD.
medullary sponge kidney (MSK) more likely to form Ca phosphate stones.

Nondietary: Age, race, body size, and environment important. (middle aged obese white man working in hot envrio)

Genetic: two most common rare monogenic disorders that lead to stone formation are primary hyperoxaluria and cystinuria (auto recessive--> abnorm reabsorption of filtered dibasic aas)

Citrate: a natural inhibitor of Ca-containing stones

Evaluation for Stone Prevention: >1/2 of first-time stone formers: recurrence within 10 yrs

P/E:... as well as signs of other systemic conditions such as primary hyperparathyroidism and gout

Clinical presentation: two common for acute stone event: renal colic and painless gross hematuria.
Renal colic is a misnomer bc pain typically doesn't subside completely; rather, it varies in intensity. When a stone moves into ureter, discomfort often begins w/ a sudden onset of unilateral flank pain. The intensity of the pain can incr rapidly,

Ca phosphate:
-more common in distal RTA + primary hyperparathyroidism.
-Thiazide diuretics (w/ Na restriction) may be used to reduce urine calciumas described above for calcium oxalate stones.
-alkali supplements (e.g., potassium citrate) may be used to increase urine citrate; However urine pH should be monitored carefully because supplemental alkali can raise urine pH--> incr risk of stone formation.
-Reduction of dietary phosphate may be beneficial by reducing urine phosphate excretion.

Ca Oxalate:
-dietary Ca restriction harmful;
-thiazide diuretic can substantially lower urine Ca excretion;
-avoid high-dose vit C supplements;
-avoidance of foods that contain high amounts of oxalate (spinach, rhubarb, and potatoes)
-Citrate is a natural inhibitor of Ca oxalate and Ca phosphate stones. Higher-level consumption of foods rich in alkali (i.e., fruits and vegetables) can increase urine citrate; addition of supplemental alkali (typically potassium citrate);
-reduce Na intake

Cystine: focus: incr cystine solubility.: treatment w/ medication that covalently binds to cystine (tiopronin and penicillamine) and a medication that raises urine pH (Tiopronin); preferred alkalinizing agent is potassium citrate as Na salts may increase cystine excretion

Struvite (also known as infection stones or triplephosphate stones):
-form only when upper urinary tract infected w/ urease-producing bacteria such as Proteus, Klebsiella--> hydrolyzes urea--> elevate urine pH to a supraphysiologic level (>8.0)--> stones may grow quickly and fill the renal pelvis (staghorn calculi).
-require complete removal by a urologist; if not, urease inhibitor acetohydroxamic acid can be considered

types of kidney stones in order of prevalence: Ca oxalate (~75%); Ca phosphate (~15%), uric acid (~8%), struvite (~1%), and cystine (<1%)

Many a mixture of crystal types (ca oxalate and ca phosphate) and also contain pr in stone matrix. Rarely, stones are composed of medications, such as acyclovir, indinavir, and triamterene.`

19% of men + 9% of women: min one stone during their lifetime. prevalence 50% lower among black than whites.
(middle aged white man)

white men: 3.5 cases/1000 at 40 (peak) and declines to ~2 cases/1000 by 70.

white women: 2.5 cases/1000 in their 30s; decr to ~1.5/1000 at 50 and beyond

supersaturation; However, even though in most individuals urine is supersaturated w/ respect to one or more types of crystals, presence of inhibitors of crystallization prevents the majority of the population from continuously forming stones

majority of ca oxalate stones grow on ca phosphate at tip of renal papilla (Randall’s plaque). process of stone formation may begin yrs before a clinically detectable stone is identified

animal pr :--> incr excretion of Ca and uric acid + decr urinary excretion of citrate--> all incr risk of stone formation.

oxalate: much of oxalate in food may not be readily absorbed. However, absorption may be higher in stone formers. urinary oxalate is a strong RF for Ca oxalate stone formation

Na + sucrose + fructose : incr Ca excretion independent of Ca intake

Ca: --> reduction in intestinal absorption of dietary oxalate; Low Ca intake is contraindicated; supplemental ca may incr risk

K: decr Ca excretion, and many K-rich foods incr urinary citrate excretion due to alkali content

Vit C supplements: possibly bc of raised levels of oxalate in urine.

vit B6 supplements: may be beneficial in pxs w/ type 1 primary hyperoxaluria

Uric acid form only when urine pH is consistently ≤5.5

Ca phosphate more likely to form when urine pH is ≥6.5

blocks ureter as it crosses over R pelvic brim--> acute appendicitis

Serum typically normal, but WBC count may be elevated.

urine sediment: u. RBC + WBC + occasionally crystals; absence of hematuria does not exclude a stone, particularly when urine flow is completely obstructed by a stone.

diagnosis often made on basis of Hx, P/E, and urinalysis--> may not be necessary to wait for radiographic confirmation before treating symptoms; diagnosis confirmed by an appropriate imaging study—preferably helical CT (highly sensitive, allows visualization of uric acid stones (traditionally considered “radiolucent”), and is able to avoid radiocontrast); plain abdominal radiograph (kidney/ureter/bladder, or KUB) can miss a stone in ureter or kidney, even if radiopaque, and does not provide info on obstruction. Abdominal ultrasound offers advantage of avoiding radiation and provides info on hydronephrosis, but not as sensitive as CT and images only kidney and possibly proximal segment of ureter; thus most ureteral stones not detectable by ultrasound.

parenteral NSAIDs (ex ketorolac) just as effective as opioids in relieving symptoms and fewer side effects.
Excessive fluid administration not shown to be beneficial;
alpha-blocker may incr rate of spontaneous stone passage (dilates ureter)

Urologic intervention postponed unless evidence of UTI, a low probability of spontaneous stone passage (e.g., a stone measuring ≥6 mm or an anatomic abnormality), or intractable pain.

Extracorporeal shockwave lithotripsy, least invasive option, to fragment the stone.
endourologic approach: remove stone by basket extraction or laser fragmentation.
For large upper-tract stones, percutaneous nephrostolithotomy

serum levels: electrolytes (hypokalemia or RTA), creatinine, Ca, and uric acid; PTH if indicated by high Ca;

examination of urine sediment: in asymptomatic residual renal stones, RBC + WBC frequently present, crystals help stone type

24-h urine collections: cornerstone on which therapeutic recommendations based.
factors measured: total volume, Ca, oxalate, citrate, uric acid, Na, K, phosphorus, pH, and creatinine

Imaging: “gold standard”: helical CT without contrast; . Although less sensitive, renal ultrasound or a KUB exam typically used to minimize radiation exposure

incr intake of foods rich in alkali (e.g., fruits and vegetables) and reducing the intake of foods that produce acid (e.g., animal flesh)

If necessary, supplementation w/ bicarbonate or citrate salts (preferably potassium citrate);

If not successful-->a xanthine oxidase inhibitor, such as allopurinol or febuxostat