Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm(3), 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72 percent were males, 59 percent had been HIV-infected for >5 years, 72 percent had CD4 counts <200 cells/mm³, 87 percent developed electrolyte disturbances, 33 percent recovered renal function, and 56 percent survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Beneficial and harmful effects of L-arginine on renal ischaemia.

BACKGROUND: The role of nitric oxide (NO) in acute renal failure (ARF) is not yet completely understood. L-Arginine (L-arg) is protective against different ARF models, while L-arg addition in isolated proximal tubules enhances hypoxia/reoxygenation (H/R) injury. The aim of this study was to evaluate the effects of L-arg on renal ischaemia. METHODS: In in vivo studies, Wistar rats were subjected to 60 min renal artery clamping, and renal function was evaluated 2 and 15 days after ischaemia. Four groups were studied: (1) control; (2) acute L-arg (50 mg/kg/bw i.v.); (3) L-nitro-arginine-methyl esther (L-NAME; 0.5 mg/kg/bw i.v.); and (4) chronic L-arg (L-arg 0.25% in drinking water/7 days). For the in vitro studies, proximal tubules (PTs), isolated by collagenase digestion and Percoll gradient, were studied from three groups: (1) untreated; (2) L-arg-treated (L-arg 0.25% in drinking water/7 days); and (3) L-NAME-treated rats (3 mg/kg in drinking water/7 days). PTs were kept oxygenated or subjected to 15 min hypoxia (H-15) and 35 min reoxygenation (R-35). In some experiments, additional doses of L-arg and L-NAME were administered. Cell injury was assessed by lactate dehydrogenase (LDH) release. NO production was evaluated by NO2-/NO3- measurement (Griess reaction) in both urine and isolation medium. RESULTS: After 2 days, L-arg infusion protected against ischaemia compared with control rats (0.4 vs 0.2 ml/min/100 g, P < 0.001), while neither L-NAME nor chronic L-arg supplementation ameliorated renal function. After 15 days, both acute and chronic L-arg groups showed a higher glomerular filtration rate (0.6 and 0.75 ml/min/100 g) compared with control rats (0.3 ml/min/100 g, P < 0.05) and L-NAME-treated rats (0.2 ml/min/100 g, P < 0.05). Despite similar recovery in both L-arg groups, the mortality rate was 25% in the chronic L-arg group. Tubular function was also better preserved in the acute L-arg group. PTs isolated from L-arg-treated rats were more sensitive to isolation injury. L-Arg addition enhanced H/R injury (44.9 vs 51.8%, P < 0.05), whereas L-NAME addition protected (44.9 vs 24%, P < 0.001) in untreated rats. In L-arg-treated rats, addition of L-arg did not enhance H/R injury (49.6 vs 53.5%, NS) and L-NAME was still protective (49.6 vs 32.3%, P < 0.001). In PTs from L-NAME-treated rats, L-arg addition also did not enhance H/R injury (50 vs 54%, NS) whereas L-NAME was protective (50 vs 27%, P < 0.001). NO2-/NO3- production paralleled L-arg and L-NAME supplementation. CONCLUSION: It was demonstrated that acute L-arg infusion was beneficial in in vivo renal ischaemia while it was harmful in isolated H/R tubules. In contrast, chronic L-arg supplementation was deleterious both in in vivo and in vitro renal ischaemia, suggesting that injurious effects had overcome the beneficial effects during excess NO exposure.

Protective effect of L-arginine on hypercholesterolemia-enhanced renal ischemic injury.

The effects of hypercholesterolemia on ischemic renal failure were evaluated in rats subjected to 60 min of left renal artery clamping and contralateral nephrectomy. One group of rats (HC) was kept on a cholesterol-supplemented diet for 3 weeks before renal injury and compared to a group fed a regular diet (ND). Two days after renal ischemia, inulin clearance (C(in), ml/min per 100 g BW) was lower in HC-rats (0.033 +/- 0.011) than in ND-rats (0.227 +/- 0.037; P < 0.01). indicating that hypercholesterolemia potentiated renal ischemic injury. Twenty-one days after renal ischemia the C(in) of HC-rats did not differ from ND-rats, suggesting that hypercholesterolemia did not limit late recovery. Since nitric oxide production is impaired in HC, L-arginine (50 mg/kg BW i.v.) was administered immediately after ischemia. Two days after ischemia, L-arg did not protect ND-rats from ischemia, while the C(in) and renal blood flow were higher in L-arg-treated HC rats than in untreated HC rats (C(in) = 0.125 +/- 0.013 rats vs. 0.033 +/- 0.011; P < 0.001) (RBF = 3.96 +/- 0.64 vs. 2.40 +/- 0.20 ml/min per 100 g BW; P < 0.05), indicating that L-arg protects HC rats from renal ischemia. The administration of D-arginine to ND rats induced a significant decrease of the C(in) and a significant increase of FE H2O, FE Na and FE K compared to the L-arginine and not treated groups. Cultures of inner medullary collecting duct cells from ND rats were resistant to 24-h hypoxia. In contrast, IMCD cell cultures from HC rats showed higher LDH release after 24-h hypoxia than normoxic cells (69.2 +/- 3.4 vs. 30.9 +/- 3.6%, P < 0.001); 1 mM L-arg added to the medium attenuated LDH release (44.3 +/- 2.4%, P < 0.01). These data demonstrate that HC predisposes renal tubular cells to hypoxic injury and L-arg protects cells of HC.

L-Arginine and allopurinol protect against cyclosporine nephrotoxicity.

The role of nitric oxide (NO) and oxygen free radicals in cyclosporine (CsA) nephrotoxicity was investigated using L-arginine, an NO substrate, and allopurinol, a xanthine oxidase inhibitor (involved in the formation of oxygen radicals) in an experimental model with Wistar rats. CsA, administered at 15 mg/kg/body weight (BW) subcutaneously for 10 days, caused a decrease in glomerular filtration rate, with inulin clearance of 0.33+/-0.04 vs. 1.11+/-0.06 ml/min/100 g BW (P<0.01 vs. control). L-Arginine, 1.5% in drinking water 5 days before and during CsA administration, partially protected the animals against this fall in glomerular filtration rate, with inulin clearance of 0.68+/-0.03 ml/min/100 g BW (P<0.01 vs. CsA). Allopurinol, at 10 mg/kg/BW by gavage, also had a protective action, with inulin clearance of 0.54+/-0.04 ml/min/100 g (P<0.01 vs. CsA). CsA caused an elevation in NO production, as assessed by urinary excretion of its metabolites, nitrite and nitrate (NO2 and NO3; 0.836+/-0.358 vs. 0.107+/-0.019 nmol/microg creatinine). NO production was as much as threefold higher in the L-arginine group (1.853+/-0.206 nmol/g creatinine). This CsA effect is probably related to its vasoconstrictive stimulus. Supplementation with L-arginine, which provides more substrate for NO formation, may enhance vasodilatation and consequently reduce the impairment of renal function. The protection provided by allopurinol may be related to the reduced formation of oxygen radicals, preventing the deleterious effects of lipid peroxidation.