Obstructive nephropathy

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

Obstructive nephropathy, central neivous system symptomatology... 

Obstructive nephropathy Intratubular obstruction OKT3 Nephrolithiasis... 

Nephrotoxicity Pre-renal failure, e.g. hypotension following 3 lactam-induced anaphylaxis Obstructive nephropathy, e.g. crystal deposition following cephalosixrin administration... 

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Loop agents can increase the rate of urine flow and enhance K+ excretion in acute renal failure. However, they do not shorten the duration of renal failure. If a large pigment load has precipitated acute renal failure (or threatens to), loop agents may help flush out intratubular casts and ameliorate intratubular obstruction. On the other hand, loop agents can theoretically worsen cast formation in myeloma and light chain nephropathy. 

Cationized gelatin has been used in vivo to mediate vector-based RNAi in a murine model of obstructive nephropathy after intraureteral delivery. Administration of a plasmid encoding siRNA against the transforming growth factor-(3 (TGF-P) receptor gene resulted in a reduction in collagen content and fibrotic... 

Kushibiki, T., Nagata-Nakajima, N., Sugai, M., Shimizu, A., and Tabata, Y. (2006) Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds. Journal of Controlled Release 110 610-617. 

Tubule obstruction. Given certain physicochemical conditions, crystals can deposit within the tubular lumen. Methotrexate, for example, is relatively insoluble at low pH and can precipitate in the distal nephron when the urine is acid. Similarly the uric acid produced by the metabolism of nucleic acids released during rapid tumour cell lysis can cause a fatal urate nephropathy. This was a particular problem with the introduction of chemotherapy for leukaemias until the introduction of allopurinol it is now routinely given before the start of chemotherapy to block xanthine oxidase so that the much more soluble uric acid precursor, hypoxanthine, is excreted instead. Crystal-nephropathy is also a... 

A 70-year-old man with advanced obstructive nephropathy began to hemorrhage from the bladder after decompression with a Foley catheter (74). He developed an encephalopathy after continuous irrigation with 1% alum for 2 days, associated with raised serum aluminium concentrations. Repeated treatment with deferoxamine and hemodialysis removed some aluminium, but he succumbed to bronchopneumonia. At autopsy his brain aluminium content was not excessive. 

Carbone LG, Bendixen B, Appel GB. Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome. Am J Kidney Dis 1988 12(l) 72-5. 

Colebunders R, Depraetere K, De Droogh E, Kamper A, Corthout B, Bottiau E. Obstructive nephropathy due to sulfa crystals in two HIV seropositive patients treated with sulfadiazine. Jbr-Btr. 1999 Aug 82(4) 153-4. 

In an in vivo animal study, at doses not causing crystalluria or tissue crystal deposition, short term exposure to acyclovir caused increased renal vasoconstriction and an associated fall in renal blood flow and single nephron plasma flow [22]. Longer-term treatment resulted in a fall in glomerular ultrafiltration coefficient. Thus, it is not clear whether the pathogenesis of acyclovir-induced AKI in humans reflects an obstructive nephropathy from intratubular precipitation of acyclovir, a hemodynamic response, or a type of toxic, immunologic, or hypersensitivity reaction. It is also possible that more than one process may be involved. 

The clinical circumstances that lead to chronic "analgesic abuse" nephropathy [111] are quite distinct to the rare occurrence of acute papillary necrosis associated with exposure of fhe patient to a single NSAID and often with only a short period of drug exposure. In these acute circumstances, the patient will typically present clinically with gross hematuria and may have flank pain suggestive of ureteric obstruction consequent to the passage of a sloughed papilla. 

Xanthine nephropathy has been reported in tumor lysis syndrome (TLS) in patients with hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme deficiency [180b], however, this patients cultured fibroblasts yielded normal levels of HGPRT enzyme. Allopurinol pretreatment allows the build up of both xanthine and hypoxanthine which, in the absence of HGPRT, cannot be recycled and thus xanthine supersaturation in the urine resulting in xanthine stones with subsequent obstructive renal failure. 

It is not known whether these changes are the result of a normal aging process (i.e., involutional) or the result of the interplay of pathology and age. Cumulative exposure to common causes of chronic kidney disease (CKD), such as (1) atherosclerosis, (2) hypertension, (3) heart failure, (4) diabetes,(5) obstructive nephropathy, (5) infection, (6) immune insult, (7) nephrotoxins such as lead, and (8) dietary protein increases with age and it is difficult to separate these effects from those of healthy aging. The decline in GFR with increasing age may be largely attributable to hypertension, atherosclerosis, or heart failure. In the absence of these or other identifiable causes of kidney disease, many older subjects have stable GFR over time. 

Diseases of the kidney that are discussed in this section include (1) the uremic syndrome, (2) chronic kidney disease, (3) end-stage renal disease, (4) diabetic nephropathy, (5) hypertensive nephropathy, (6) glomerular diseases, (7) interstitial nephritis, (8) polycystic Iddney disease, (9) polycystic kidney disease, (10) toxic nephropathy, (11) obstructive uropathy, (12) tubular diseases, (13) renal calculi, and (14) cystinuria. In addition, this section also includes discussions on (1) prostaglandins and NS AIDS in kidney disease, (2) monoclonal light chains and kidney disease, and (3) urinary osmolality. 

Selective Aldosterone Deficiency (Type IV RTA). In type IV RTA, there is failure of distal potassium and hydrogen ion secretion because of aldosterone deficiency or resistance. This may occur because of a range of steroid or steroid receptor synthetic defects or because of hyporeninemic hypoaldosteronism (e.g., due to diabetic nephropathy, tubulointerstitial disease, urinary obstruction, renal transplantation, or SLE). Hyperkalemia, although mild, is a usual manifestation. 

Renal Tubular Acidoses, Types I and II These syndromes are predominantly characterized by loss of bicarbonate because of decreased tubular secretion of (distal or type I RTA) or decreased reabsorption of HCO3 (proximal or type II RTA). Because the major urine-acidifying power of the kidneys rests in the distal tubules, the proximal and distal RTAs may be differentiated by measurement of urine pH. In proximal RTA, urine pH becomes <5.5, whereas in distal RTA the distal tubules are compromised and urine pH is >5.5. When distal RTA is associated with obstructive nephropathy, sickle cell disease, or systemic lupus erythematosus, hyperkalemia may... 

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