Tubulointerstitial nephropathy

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D Agati VD. Lithium nephrotoxicity a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol 20(X) 11 (8) l 439 t8. 

Various forms of renal damage, notably tubulointerstitial nephropathy, have been associated with long-term use of high dosages of ascorbic acid, for example 3 g/day (31). 

Nakamoto Y, Motohashi S, Kasahara H, Numazawa K. Irreversible tubulointerstitial nephropathy associated with prolonged, massive intake of vitamin C. Nephrol Dial Transplant 1998 13(3) 754-6. 

Martinez E, Mommeja-Marin FI, Estepa-Maurice L, Beaufils FI, Boche, M, Daudon M, Deray G, and Katlama C. 1998. Indinavir crystal deposits associated with tubulointerstitial nephropathy. Nephrol Dial Transplant 13 750-753. 

Appel GB, Kunis C.L. Acute interstitial nephriitis. In Cotran RS BB, Stein JFI, ed. Tubulointerstitial nephropathies. NewYork Churchill 1983 151-85. 

Eknoyan. Acute renal failure associated with tubulointerstitial nephropathies. In Brenner BM U,ed. Acute Renal Failure. 2nd ed. New York Churchill Livingstone 1988 491-534. 

Appel GB, Kunis CL. Acute interstitial nephritis. In Tubulointerstitial nephropathies. Cotran RS, Brenner BM, Stein JEI (editors). Churchill, New York 1983 p. 151-185. 

Richmond et al. (1979) report nephrotoxic effects of cotrimoxazole, and Dry et al. (1975) a case of acute tubulointerstitial nephropathy. 

Bennett WM, Elzinga LW, Porter GA. Tubulointerstitial disease and toxic nephropathy. In The kidney. Brenner BM, Rector FC Jr (editors). WB Saunders, Philadelphia 1991 p 1430-1496. 

Viscosity of THP solutions increases markedly when the sodium chloride concentration is > 60 mM. Increasing the concentration of calcium and/.or a reduction in pH also increase viscosity and may account for the involvement of THP in the pathogenesis of cast nephropathy and tubulointerstitial nephritis. THP appears to have an inhibitory effect on urinary crystal arrgegation [154] and may play a role in preventing renal stone formation [155]. In some humans with calcium oxalate nephrolithiasis, a molecular abnormality of THP has been detected [156]. Other studies showed decreased urinary levels of THP in patients with nephrolithiasis [157, 158]. A relative deficiency in THP has been associated with impaired inhibition of crystal adhesion to renal epithelial cells instone formers [159]. 

Extensive expression of KlM-1 has been found in proximal tubule cells in biopsies from patients with acute tubular necrosis [302]. KlM-1 is also expressed in other conditions where proximal tubules are dedifferentiated, including renal cell carcinoma [303, 304], chronic cyclosporine nephrotoxicity [305], a protein-overload model of tubulointerstitial disease [306], polycystic kidney disease [307], and contrast nephropathy. In several chronic conditions, KlM-1 has been found primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis and inflammation. Independent of the specific disease, renal KIM-1 correlated positively with the extent of renal damage and negatively with renal function. In these patients, urinary levels of KIM-1 were and correlated positively with tissue KIM-1 and negatively with renal function. Thus, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. Urinary KIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1. 

In one case of tubulointerstitial nephritis and nephrotic syndrome induced by Triazolam, a sleep inducer numerous eosinophils [85] were found to infiltrate glomeruli and interstitium suggesting that eosinophils may be pathogenic in this situation. An association with tubulointerstitial nephritis and nephrotic syndrome has also been occasionally reported for penicillin/ amoxicillin induced nephropathies [86]. Several reports have analyzed T-cells in penicillin-induced allergy. CD4 T-cells specific for penicillin may be derived from the patients and produce mainly lL-5, some of them being perforin positive with a cytolytic potential [87]. 2) P-lactam specific clones may be obtained only from patients with adverse reactions the clones were Th2 whatever the type of clinical manifestations and... 

Figure 1, Renal biopsy of patient with heroin nephropathy showing focal glomerulosclerosis plus severe tubulointerstitial damage.

ElzingaLW, Rosen S, BennettWM. Dissociation of glomerular filtration rate from tubulointerstitial fibrosis in experimental chronic cyclosporine nephropathy role of sodium intake. J Am Soc Nephrol 1993 4 214-221. 

Balkan (or endemic) nephropathy is a chronic tubulointerstitial disease of unknown, presumably exotoxic etiology. It has been shown to exist only in some parts of the southeastern Europe. 

Balkan nephropathy is non-destructive and noninflammatory tubulointerstitial renal disease [69]. The changes are non-specific and in the chronic, sclerotic phase they may be quite similar to changes observed in other chronic interstitial diseases such as analgesic nephropathy [70], vascular nephrosclerosis [69] cyclosporine-induced nephropathy [71], radiation nephritis [72,73] and aging [72], intoxication with silicate, cadmium, lead, uranium [74], mycotoxin ochratoxin... 

Recently similarity of Balkan nephropathy and nephropathy induced by Chinese herbs used in slimming diets have been suggested [48]. Nevertheless, Chinese herb nephropathy is rapid progressive tubulointerstitial diseases with pronounced fibrosis and progression towards end-stage renal disease within few years, clearly different from the protracted clinical course of Balkan nephropathy. 

---