Timing Of Acute Kidney Injury Research Articles

Temporal Relationship and Clinical Outcomes of Acute Kidney Injury Following Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18-0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71-2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24-6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19-1.8). However, the certainty of evidence for most outcomes was low to very low. While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation.

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.

Timing and Degree of Acute Kidney Injury in Patients Requiring Non-Surgical Intensive Care.

The degree and timing of acute kidney injury (AKI) on admission and during hospitalization in patients requiring non-surgical intensive care remain unclear. In this study, 3,758 patients requiring intensive care were analyzed retrospectively. AKI was defined based on the ratio of serum creatinine concentrations recorded at each time point (i.e., on admission and during the first 5 days in the intensive care unit and during hospitalization) to those measured at baseline. Patients were grouped by combining AKI severity (RIFLE class) and timing (i.e., from admission to 5 days [A-5D]; from 5 days to hospital discharge [5D-HD]) as follows: No-AKI; New-AKI (no AKI to Class R [risk; ≥1.5-fold increase in serum creatinine], I [injury; ≥2.0-fold increase in serum creatinine], and F [failure; ≥3.0-fold increase in serum creatinine or receiving dialysis during hospitalization]); Stable-AKI (Class R to R; Class I to I); and Worsening-AKI (Class R to I or F; Class I to F). Multivariate logistic regression analysis indicated that 730-day mortality was independently associated with Class R, I, and F on admission; Class I and F during the 5D-H period; and New-AKI and Worsening-AKI during A-5D and 5D-HD. AKI on admission, even Class R, was associated with a poor prognosis. An increase in RIFLE class during hospitalization was identified as an important factor for poor prognosis in patients requiring intensive care.

Ferritin and procalcitonin in COVID-19 associated acute kidney injury – gender disparities, but similar outcomes

Abstract Background: Acute kidney injury is a severe complication of COVID-19. Both COVID-19 and related acute kidney injury are reported in the literature to be more prevalent and more severe in males. Methods: We performed a retrospective analysis of the COVID-19 associated acute kidney injury cases in order to search for differences between genders regarding patients’ and renal outcome. Results: 250 patients with acute kidney injury were included in the study: 93 women (37.20%), 157 men (62.80%). There were no differences between sexes regarding age. Diabetes mellitus was significantly more present in women. Peak ferritin and procalcitonin levels were significantly higher in men, but other severity markers for COVID-19 did not differ between genders. There were no differences between sexes regarding history of chronic kidney disease, timing of acute kidney injury, need for dialysis or recovery of renal function. ICU admission and in-hospital mortality were similar between men and women. Conclusions: In our study, COVID-19 related-AKI was more prevalent in men than in women, but the patients’ and renal outcome were similar. Significantly higher ferritin and procalcitonin serum levels registered in male patients when compared to women may have additional explanations beside more severe SARS-CoV-2 infection in males.

Timing of AKI after urgent percutaneous coronary intervention and clinical outcomes: a high-dimensional propensity score analysis

IntroductionAcute kidney injury is a common complication of percutaneous coronary intervention and has been associated with an increased risk of death and progressive chronic kidney disease. However, whether the timing of acute kidney injury after urgent percutaneous coronary intervention could be used to improve patient risk stratification is not known.MethodsWe conducted a retrospective cohort study in adults surviving an urgent percutaneous coronary intervention between 2008 and 2013 within Kaiser Permanente Northern California, a large integrated healthcare delivery system, to evaluate the impact of acute kidney injury during hospitalization at 12 (±6), 24 (±6) and 48 (±6) hours after urgent percutaneous coronary intervention and subsequent risks of adverse outcomes within the first year after discharge. We used multivariable Cox proportional hazards models with adjustment for a high-dimensional propensity score for developing acute kidney injury after percutaneous coronary intervention to examine the associations between acute kidney injury timing and all-cause death and worsening chronic kidney disease.ResultsAmong 7250 eligible adults undergoing urgent percutaneous coronary intervention, 306 (4.2%) had acute kidney injury at one or more of the examined time periods after percutaneous coronary intervention. After adjustment, acute kidney injury at 12 (±6) hours was independently associated with higher risks of death (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 2.19–5.75) and worsening kidney function (aHR 2.40, 95% CI:1.24–4.63). Similar results were observed for acute kidney injury at 24 (±6) hours and death (aHR 3.90, 95% CI:2.29–6.66) and worsening chronic kidney disease (aHR 4.77, 95% CI:2.46–9.23). Acute kidney injury at 48 (±6) hours was associated with excess mortality (aHR 1.97, 95% CI:1.19–3.26) but was not significantly associated with worsening kidney function (aHR 0.91, 95% CI:0.42–1.98).ConclusionsTiming of acute kidney injury after urgent percutaneous coronary intervention may be differentially associated with subsequent risk of worsening kidney function but not death.

The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury \u2013 a pilot study

BackgroundIn the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients. Remarkable changes in the urinary metabolome occur during AKI, which may influence the urinary microbiome. To our knowledge, this is the first study that examines the urinary microbiome in renal transplant recipients (RTX) and non-transplant recipients (nRTX) at time of AKI.MethodsIn this cross-sectional pilot-study the urinary microbiome of 21 RTX and 9 nRTX with AKI was examined. Clean catch morning urine samples were obtained from all patients on the first day of AKI diagnosis. AKI was defined according to KDIGO guidelines. Urinary microbiota and the urinary metabolome during AKI were assessed in one patient. 16S rRNA sequencing was performed. Sequences were processed using UPARSE-pipeline for operational taxonomic units (OTU) and taxon finding.ResultsWe successfully extracted and sequenced bacterial DNA from 100% of the urine samples. All 30 patients revealed at least 106,138 reads. 319 OTU and 211 different genera were identified. The microbiotic diversity richness in the RTX group was no different from the nRTX group. Eighteen genera were solely present in nRTX and 7 in RTX.ConclusionsThe urinary microbiome at time of AKI showed different bacterial genera in RTX compared to nRTX. The nRTX group exhibited no different diversity to the RTX group. Irrespective of the status of a previous renal transplantation, the urinary microbiome comprised > 210 different genera. An intraindividual change in microbiota diversity and richness was observed in one study patient during recovery from AKI.

The effect of resolution time of acute kidney injury on clinical outcomes.

Acute kidney injury (AKI) is a frequent and complex disease. It is not clearly defined whether its duration is related to adverse outcomes. We determined the effect of AKI resolution time on patient's clinical outcomes. A prospective cohort of hospitalized patients with AKI by AKI network (AKIN) creatinine criteria was included. Variables for prognosis and follow-up were analyzed. One hundred and thirteen patients were included in the study. Seventy-seven (68.1%) were males, mean age 55 years (range, 16–76 years), and 48 (42.5%) were diabetic. The most common cause of AKI was sepsis (31%). AKI resolution time ≤2 days and >2 days was seen in 47 (41.6%) and 66 (58.4%) of the cases, respectively. AKI resolution time >2 days was common in older patients (66.24 ± 17.6 year vs. 47.16 ± 12.32 year, P = 0.004), with the use of mechanical ventilation (27% vs. 4%, P = 0.02) and vasopressors (41% vs. 11%, P ≤ 0.01); it was associated with increased mortality (47% vs. 4%, P ≤ 0.01), and a discharge estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (52% vs. 2%, P = 0.01), than in patients with resolution time ≤2 days. Survival rate was significantly worse in patients with a resolution time >2 days. By multivariate logistic step-wise regression analysis, AKI >2days, vasopressor use, and AKIN stage 2–3 were independently associated with higher mortality. AKI >2 days and vasopressor utilization were independently associated to an eGFR <60 ml/min/1.73 m2 at the time of discharge. We conclude that AKI resolution time >2 days is linked to adverse clinical outcomes.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group.

In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). Multicenter retrospective observational cohort study. Six pediatric extracorporeal membrane oxygenation centers. Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. None. Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKI) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKI). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKI and 65% AKI) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKI) and 93% (AKI). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKI, 152 vs 110 hr; AKI, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKI: odds ratio, 1.77; 1.22-2.55 and AKI: odds ratio, 2.50; 1.61-3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKI, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKI: odds ratio, 1.52; 1.04-2.21). Acute kidney injury is present in 60-74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86-93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.

Immune profile of IgA-dominant diffuse proliferative glomerulonephritis.

The diagnosis of IgA-dominant post-infectious glomerulonephritis (PIGN) may be challenging, as it must be differentiated from that of active IgA nephropathy. Predominant clinicopathologic features of IgA-dominant PIGN substantially overlap with those of active IgA nephropathy. Here, we present a case of a 67-year-old woman with rapidly rising serum creatinine, proteinuria and severe hypertension. The kidney biopsy findings included some features of IgA-dominant PIGN while others were more consistent with classical IgA nephropathy. We describe this patient's immune profile at the time of acute kidney injury and review the literature regarding differentiation of the two entities.

Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure.

Since acute kidney injury (AKI) is not always related to mortality in patients with acute decompensated heart failure (ADHF), the aim of this study was to focus on onset time of AKI and its clinical importance. A total of 371 ADHF patients were included. The impact of AKI (≥ 0.3 mg/dl or 1.5-fold increase in serum creatinine level within 48 h) with early onset (≤ 4 days from admission) or late onset (≥ 5 days from admission) was assessed. AKI occurred in 99 patients, who were divided into two groups according to the median onset time of AKI: 50 with early onset of AKI and 49 with late onset of AKI. The maximum increase in serum creatinine level from admission was greater in patients with late onset of AKI than in patients with early onset of AKI (p = 0.012). Patients with late onset of AKI had a higher 12-month mortality rate than that in patients with early onset of AKI (log-rank test, p = 0.014). Late onset of AKI was an independent predictor of mortality (hazard ratio: 3.39, 95 % confidence interval: 1.84-6.18, p < 0.001). Late onset of AKI was associated with high blood urea nitrogen level at admission and intravenous administration of dobutamine. In conclusion, late onset of AKI related to high blood urea nitrogen level and intravenous administration of dobutamine, but not early onset of AKI, is linked to high mortality rate. Onset time of AKI may be useful for risk stratification of mortality in ADHF patients developing AKI.

Timing of acute kidney injury — does it matter? A single-centre experience from the United Kingdom

BackgroundAcute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high mortality and long-term dependence on RRT. However, there is limited information about the difference in outcome between patients who develop AKI in the community (c-AKI), and those who develop AKI in hospital (h-AKI). AimIdentify differences in short- and long-term outcomes between patients admitted with c-AKI and h-AKI who require intermittent haemodialysis, and to identify factors that predict poor outcome. Design & methodsSingle-centre, retrospective analysis of 306 patients with AKI who received intermittent haemodialysis between 2009 and 2011. Follow-up: six months. Primary endpoints: patient and renal survival. Secondary endpoints: time on dialysis, length of hospital stay, and admission to the intensive care unit (ICU). ResultsSurvival for patients in the h-AKI group was significantly lower, at 42.9% (compared to 72%). They had a significantly longer length of stay. However, at 6-month follow-up, the survival benefit of the c-AKI group was no longer significant. Patients with h-AKI were more likely to be dialysis independent at discharge and six months although this result did not reach statistical significance. Independent predictors of survival to discharge within the entire group included: renal/post-renal causes of AKI, younger age, pre-existing diabetes, and c-AKI. The only independent predictor for RRT dependence at discharge and six months was pre-existing chronic kidney disease. Conclusionsh-AKI is associated with high mortality and longer hospital stays during the acute admission. However, h-AKI patients who survive are more likely to be independent of RRT at discharge and follow-up.

Urinary KIM-1, IL-18 and Cys-c as early predictive biomarkers in gadolinium-based contrast-induced nephropathy in the elderly patients

This study was designed to investigate whether urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and cystatin C (Cys-C) are early predictive biomarkers for gadolinium-based contrast-induced nephropathy (Gd-CIN) in the elderly patients undergoing gadolinium-enhanced magnetic resonance imaging (MRI). 60 elderly patients undergoing enhanced MRI using gadolinium-based contrast media were enrolled. Urine samples were collected before and 24 hours and 48 hours after the procedure, and KIM-1, IL-18 and Cys-C levels were measured by using an ELLSA kit respectively. Serum samples before and 24 hours and 48 hours after the procedure were also collected, and creatinine was measured by automatic biochemical analyzer. Gd-CIN was diagnosed in 8 of 60 (13.3%) patients. At 24 hours after MRI with gadolinium administration in the Gd-CIN group, the urinary KIM-1, IL-18 and Cys-C were significantly increased. Logistic regression analysis showed that urinary KIM-1 and IL-18 at 24 hours after gadolinium injection were independent predictive markers of Gd-CIN. The predictable time of acute kidney injury (AKI) onset determined by urinary KIM-1, IL-18 and Cys-C was 24 hours earlier than by serum creatinine. Urinary KIM-1, IL-18 and Cys-C could be early predictive biomarkers of Gd-CIN in the elderly patients, which showed a good performance in early diagnosis of Gd-CIN as compared with serum creatinine.

The impact of anemia on renal recovery and survival in acute kidney injury

Anemia occurs frequently among patients who develop acute kidney injury likely due to abnormal erythropoietic activity. Anemia has been associated with increased mortality among hospitalized patients, but its impact on renal recovery or survival is poorly characterized among patients with acute kidney injury. We aim to assess if anemia is associated with lower renal recovery and poorer survival. A retrospective cohort of 211 patients was examined. Anemia and other patient characteristics were assessed as potential risk factors for the presence of renal recovery or death. Additionally, renal recovery, dialysis requirement and survival were compared between those with mild versus severe anemia. 86% of patients with acute kidney injury (AKI) developed acute anemia which generally occurred at the time of acute kidney injury. Anemia did not appear to be associated with lack of renal recovery or death, but rather underlying comorbid conditions and severity of illness were more likely to be associated with renal recovery or death, respectively. Neither renal recovery nor survival differed among patients with mild versus severe anemia as measured by fall in hemoglobin or nadir hemoglobin. New onset anemia does not appear to be associated with lack of renal recovery or death among patients with acute kidney injury.

A comparison of four methods to define timing of acute kidney injury

RIFLE provides standardized criteria for defining acute kidney injury (AKI) [1]. It is based on changes in serum creatinine (sCr), in relation to a premorbid sCr, and on urine output. When premorbid sCr is unknown, baseline sCr is estimated. Often only sCr is used (RIFLEcreat). Thus there are four methods for defining AKI: actual RIFLE, actual RIFLEcreat, estimated RIFLE and estimated RIFLEcreat. There is much interest for biomarkers predicting early AKI [2]. Critical for determining a biomarker's performance of AKI is the diagnosis of the first day of AKI (AKI-0). We compared the impact of four AKI definitions on determining AKI-0.

Sirolimus (Rapamycin) Induced Proteinuria in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplant

Proteinuria and renal dysfunction have been reported in patients receiving sirolimus after renal (1) or islet cell transplants (2). We report the case of a 28-year-old man undergoing allogeneic hematopoietic stem cell transplantation who suffered acute kidney injury with nephrotic range proteinuria after initiation of sirolimus. This patient with anaplastic large cell lymphoma in complete remission by positron emission tomography scan was admitted for an allogeneic hematopoietic stem cell transplant from a molecularly human leukocyte antigen-matched unrelated female donor. Four months before admission, the patient had a creatinine clearance (24 hr urine collection) of 106 mL/min and 1 month before admission had a clearance of 115 mL/min. During those outpatient visits, the patient had no protein detected by urinalysis. As part of his treatment for lymphoma, the patient received 4 monthly treatments with cisplatin and cytarabine. The last dose of cisplatin was administered 30 days before admission. Graft-versus-host disease prophylaxis consisted of sirolimus (12 mg load followed by 4 mg orally per day) and tacrolimus (0.3 mg/kg intravenous continuous infusion). At the time graft-versus-host disease prophylaxis was initiated, the patient had been on the following antibiotics in the hospital: piperacillin/ tazobactam, amikacin, and micafungin for 4 days; voriconazole for 2 days and vancomycin for 1 day. Eight days after initiation of sirolimus, blood urea nitrogen rose from 9 to 29 mg/dL and creatinine from 0.8 to 1.5 mg/dL. The tacrolimus level initially was 1.8 ng/mL, peaked at 8.6 ng/mL, but was 3.6 ng/mL during the time of acute kidney injury. The sirolimus level was initially 2.1 ng/mL, and 4.3 ng/mL during the time of acute kidney injury. The urine was cloudy and foamy and contained a jelly-like substance. Urinalysis showed 3+ protein and few white cells, and a random urine protein-to-creatinine ratio was 17. Triglycerides increased from 148 to 327 mg/dL. Albumin fell from 4.6 to 3.0 g/dL. After addition of sulfosalicylic acid the urine precipitated proteinaceous casts within seconds. Urine protein electrophoresis displayed a nonselective pattern with all fractions elevated. The creatinine peaked at 3.6 mg/dL. Sirolimus was discontinued, while tacrolimus prophylaxis was maintained. The blood urea nitrogen and creatinine improved over 3 to 4 days. The urinary protein-to-creatinine ratio declined from 17 to less than 0.5 over 2 days. Currently, patient is maintained on tacrolimus without any proteinuria and a creatinine of 0.9 mg/dL. Sirolimus has been associated with high-range proteinuria when used as replacement therapy for calcineurin inhibitors in chronic allograft nephropathy (3). Urinary protein loss presumably results from reduced tubular protein reabsorption (1). A specific pattern of renal injury has also been noted in rat models with increased intratubular cast formation, increased tubular epithelial cell proliferation, and protein endocytosis, causing massive proteinuria (4). Renal transplant patients treated with sirolimus have rarely developed intratubular casts indistinguishable from myeloma cast nephropathy. Histologically, these casts have been composed of renal tubular epithelial cells (1). Alternatively, there is speculation that sirolimus induced proteinuria is related to collapsing focal segmental glomerulosclerosis associated with vascular endothelial growth factor over-expression in podocytes (5). Senior et al. (2) have reported sirolimus related proteinuria in a nontransplanted kidney before. There was resolution of proteinuria from the native kidneys when sirolimus was discontinued in some patients with islet cell transplant. We present another case of sirolimus-related renal dysfunction and proteinuria but in a patient undergoing allogeneic hematopoietic stem cell transplantation. There was no evidence of underlying kidney disease in this patient given normal creatinine clearance and absence of proteinuria before administration of sirolimus. This patient did receive other medications that could be nephrotoxic, including tacrolimus, cisplatin, and several antibiotics. Though these medications could have contributed to the patient’s renal toxicity, the time course and dosages were not consistent with their being the primary cause of his nephrotic syndrome and acute onset of kidney injury. Because the tacrolimus levels were in the lower range of normal during the kidney insult, and because renal function recovered after cessation of sirolimus while the tacrolimus was maintained, this drug was not considered a major contributor. Similar reports of sirolimus-induced proteinuria have occurred only in renal transplant cases where the diagnosis often has been confounded by graft rejection or recurrence of the primary kidney disease. This case demonstrates a direct toxic effect of sirolimus on a nontransplanted kidney without prior tubular or glomerular disease. Kenar D. Jhaveri Division of Nephrology and Hypertension New York Presbyterian Hospital at Weill Cornell Medical Center New York, NY Jonathan H. Schatz Medical Oncology-Department Memorial Sloan-Kettering Cancer Center New York, NY James W. Young Division of Bone Marrow Transplantation Memorial Sloan-Kettering Cancer Center New York, NY Carlos Flombaum Division of Nephrology Memorial Sloan-Kettering Cancer Center New York, NY