Excessive elevation of serum phosphate during tumor lysis syndrome: Lessons from a particularly challenging case.

Burkitt's lymphoma is a common cause of tumor lysis syndrome (TLS) and, in the era of aggressive utilization of prophylactic allopurinol and recombinant uricase enzyme, nephrologists are increasingly witnessing monovalent or divalent cation abnormalities without marked uric acid elevation. An 18-year-old male received his 1st cycle of intensive chemotherapy for Burkitt's lymphoma and developed TLS as defined by the Cairo Bishop criteria. Lactate dehydrogenase peaked at 9,105 U/L (range: 130 - 250) and was accompanied by acute kidney injury, including serum creatinine 2.2 mg/dL on the 4th day with oliguria, hyperkalemia, extreme hyperphosphatemia (21.4 mg/dL), hypermagnesemia, and hypocalcemia. Renal replacement therapy decision was made based on life-threatening electrolyte disturbances. The competing necessity to effectively control hyperphosphatemia and avoid the complication of dialysis disequilibrium syndrome prompted us to perform an initial intermittent hemodialysis with simultaneous intravenous mannitol administration, followed by continuous hemodialysis to manage the continued production of phosphorus from cell lysis. Osmotic stability during the therapy session was affirmatively demonstrated (322, 319 mOsm/kg, respectively). The patient showed excellent tolerance for these therapies and eventually recovered renal function as demonstrated during follow-up visits.

Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients.

BACKGROUND: Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. METHODS: We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the US Food and Drug Administration (FDA) Guidance for industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. RESULTS: For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared with recommended dosages based on the level of estimated kidney function, 3-19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. CONCLUSIONS: The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing-related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.

Performance of creatinine and cystatin C GFR estimating equations in an HIV-positive population on antiretrovirals.

OBJECTIVE: To evaluate the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, and creatinine-cystatin C estimating equations in HIV-positive patients. METHODS: We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012, and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared with GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. RESULTS: Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV viral load. Mean (SD) measured GFR (mGFR) was 87 (26) mL/min per 1.73 m. All CKD-EPI equations performed better than the MDRD Study equation. All 3 CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation, and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. CONCLUSIONS: The CKD-EPI cystatin C equation does not seem to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study.

Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care.

OBJECTIVE: To examine long-term effects of antiretroviral therapy (ART) on kidney function, we evaluated the incidence and risk factors for chronic kidney disease (CKD) among ART-naive, HIV-infected adults and compared changes in estimated glomerular filtration rates (eGFR) before and after starting ART. METHODS: Multicenter observational cohort study of patients with at least one serum creatinine measurement before and after initiating ART. Cox proportional hazard models, and marginal structure models examined CKD risk factors; mixed-effects linear models examined eGFR slopes. RESULTS: Three thousand, three hundred and twenty-nine patients met entry criteria, contributing 10 099 person-years of observation on ART. ART was associated with a significantly slower rate of eGFR decline (from -2.18 to -1.37 ml/min per 1.73 m per year; P = 0.02). The incidence of CKD defined by eGFR thresholds of 60, 45 and 30 ml/min per 1.73 m was 10.5, 3.4 and 1.6 per 1000 person-years, respectively. In adjusted analyses black race, hepatitis C coinfection, lower time-varying CD4 cell count and higher time-varying viral load on ART were associated with higher CKD risk, and the magnitude of these risks increased with more severe CKD. Tenofovir and a ritonavir-boosted protease inhibitor (rPI) was also associated with higher CKD risk [hazard odds ratio for an eGFR threshold <60 ml/min per 1.73 m: 3.35 (95% confidence interval (CI) = 1.40-8.02)], which developed in 5.7% of patients after 4 years of exposure to this regimen-type. CONCLUSION: ART was associated with reduced CKD risk in association with CD4 cell restoration and plasma viral load suppression, despite an increased CKD risk that was associated with initial regimens that included tenofovir and rPI.

Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia-a new context for refeeding syndrome?

High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.

Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia.

OBJECTIVE: To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in an urban African setting. DESIGN: Open cohort evaluation. METHODS: We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease equation, and serum creatinine. RESULTS: From April 2004 to September 2007, 25 779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 ml/min), 23.4% moderate (30-59 ml/min), and 3.1% severe (<30 ml/min). Risk for mortality at or before 90 days was elevated for those with mildly [adjusted hazard ratio (AHR)(1/4)1.7; 95% confidence interval (95% CI)(1/4)1.5-1.9], moderately (AHR(1/4)2.3; 95% CI(1/4)2.0-2.7), and severely (AHR(1/4)4.3; 95% CI(1/4)3.1-5.5) reduced creatinine clearance. Mild (AHR(1/4)1.4; 95% CI(1/4)1.2-1.6), moderate (AHR(1/4)1.9; 95% CI(1/4)1.5-2.3), and severe (AHR(1/4)3.6; 95% CI(1/4) 2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared with those with normal renal function. Trends were similar when renal function was estimated with Modification of Diet in Renal Disease or serum creatinine. CONCLUSION: Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir--a drug with known nephrotoxicity--has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pretreatment assessment.

Arteriovenous access outcomes in haemodialysis patients with HIV infection.

BACKGROUND: Arteriovenous (AV) grafts in haemodialysis patients usually fail due to thrombosis or infection. There is limited information on whether graft outcomes in HIV-positive haemodialysis patients differ from those in HIV-negative controls. METHODS: Using a prospective, computerized vascular access database, we identified retrospectively 15 HIV-positive dialysis patients having a graft placed during a 6.5-year period (January 1999 to June 2005), and compared their graft outcomes to those observed in 30 age-, sex- and access date-matched HIV-negative control patients. In addition, the outcomes of AV fistulas in 23 HIV-positive patients were compared with those observed in 32 matched HIV-negative controls. RESULTS: Thrombosis-free graft survival was substantially worse among the HIV-positive patients than in the HIV-negative controls (1-year survival, 17% vs 62%). The hazard ratio for graft thrombosis in the HIV-positive patients was 3.22 (95% CI, 1.66-10.32, P = 0.002). Infection-free graft survival was also lower in HIV-positive patients (hazard ratio 3.51; 95% CI, 1.21-18.85, P = 0.025). Finally, cumulative graft survival (from creation until permanent failure) tended to be lower in HIV-positive patients (1 year survival, 41% vs 65%, P = 0.07). The primary failure rate of fistulas (those never usable for dialysis) was similar in HIV-positive patients and in their controls (44% vs 41%, P = 0.83). Cumulative fistula survival was similar for HIV-positive and negative patients (hazard ratio 1.32; 95% CI, 0.65-3.58, P = 0.33). CONCLUSION: AV grafts have inferior outcomes in HIV-positive patients as compared with HIV-negative patients, whereas fistulas have a similar survival in both groups.

Catheter-related bacteraemia in haemodialysis patients with HIV infection.

BACKGROUND: Tunnelled catheters are used for dialysis in over 25% of haemodialysis (HD) patients and are a major risk factor for bacteraemia. HIV-positive patients may be at particularly increased risk of catheter-related bacteraemia (CRB) due to their immunocompromised state. The present case-controlled study compared catheter-related bacteraemia with HIV-positive and HIV-negative haemodialysis patients. METHODS: Using a prospective computerized vascular access database, we identified 33 HIV-positive haemodialysis patients who had a tunneled dialysis catheter placed during a 6.5-year period. Their catheter outcomes were compared with those observed in 55 age-, sex- and access date-matched control haemodialysis patients. RESULTS: The two groups were similar in terms of age, sex, diabetes, hypertension and peripheral vascular disease, but the HIV patients were more likely to be black (94 vs 76%, P=0.03). CRB occurred in 52% of the HIV patients and 49% of the controls (P=0.83). The median infection-free catheter survival was similar in HIV-positive and negative patients (165 vs 119 days, P=0.12). Among patients with CRB, the likelihood of a Gram-negative infection was similar in both groups (18 vs 30%, P=0.37). However, polymicrobial CRB was more likely in HIV patients (41 vs 15%, P=0.049). HIV-positive patients were more likely to be hospitalized for treatment of CRB than HIV-negative patients (29 vs 7%, P=0.05). CONCLUSION: CRB is equally likely in HIV-positive and control haemodialysis patients. However, CRB is likely to be more severe in HIV-positive patients, as judged from the greater likelihood of polymicrobial infection and of hospitalization.

Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution.

BACKGROUND: Tunneled dialysis catheters are complicated by frequent systemic infections. Standard therapy of catheter-associated bacteremia involves both systemic antibiotics and catheter replacement. Recent data suggest that biofilms in the catheter lumen are responsible for the bacteremia, and that instillation of an antibiotic lock (highly concentrated antibiotic solution) into the catheter lumen after dialysis sessions can eradicate the biofilm. METHODS: We analyzed prospectively the efficacy of an antibiotic lock protocol, in conjunction with systemic antibiotics, for treatment of patients with dialysis catheter-associated bacteremia without catheter removal. Protocol success was defined as resolution of fever and negative surveillance cultures one week following completion of the protocol. Protocol failure was defined as persistence of fever or surveillance cultures positive for any pathogen. In addition, infection-free catheter survival was compared to that observed in institutional historical control patients treated with catheter replacement. RESULTS: Blood cultures were positive in 98 of 129 of episodes (76%) in which patients dialyzing with a catheter had fever or chills. Protocol success occurred in 40 of 79 infected patients (51%) treated with the antibiotic lock. Protocol failure occurred in 39 cases (49%): 7 had persistent fever, 15 had positive surveillance cultures (9 for Candida and 6 for bacteria), and 17 required catheter removal due to malfunction. Each of the pathogens in the surveillance cultures was different from the original pathogen in that patient. Eight of the 9 secondary Candida infections and all 6 secondary bacterial infections resolved after catheter exchange and specific antimicrobial treatment. Overall catheter survival with the antibiotic lock protocol was similar to that observed among patients managed with catheter replacement (median survival, 64 vs. 54 days, P = 0.24). CONCLUSIONS: Use of an antibiotic lock, in conjunction with systemic antibiotic therapy, can eradicate catheter-associated bacteremia while salvaging the catheter in about one half of cases. Moreover, this management approach offers clinical advantages over routine catheter exchange.