Leslie Rocher

Acute Renal Failure After Coronary Intervention: Incidence, Risk Factors, and Relationship to Mortality

PURPOSEnThis study set out to define the incidence, predictors, and mortality related to acute renal failure (ARF) and acute renal failure requiring dialysis (ARFD) after coronary intervention.nnnPATIENTS AND METHODSnDerivation-validation set methods were used in 1,826 consecutive patients undergoing coronary intervention with evaluation of baseline creatinine clearance (CrCl), diabetic status, contrast exposure, postprocedure creatinine, ARF, ARFD, in-hospital mortality, and long-term survival (derivation set). Multiple logistic regression was used to derive the prior probability of ARFD in a second set of 1,869 consecutive patients (validation set).nnnRESULTSnThe incidence of ARF and ARFD was 144.6/1,000 and 7.7/1,000 cases respectively. The cutoff dose of contrast below which there was no ARFD was 100 mL. No patient with a CrCl > 47 mL/min developed ARFD. These thresholds were confirmed in the validation set. Multivariate analysis found CrCl [odds ratio (OR) = 0.83, 95% confidence interval (CI) 0.77 to 0.89, P <0.00001], diabetes (OR = 5.47, 95% CI 1.40 to 21.32, P = 0.01), and contrast dose (OR = 1.008, 95% CI 1.002 to 1.013, P = 0.01) to be independent predictors of ARFD. Patients in the validation set who underwent dialysis had a predicted prior probability of ARFD of between 0.07 and 0.73. The in-hospital mortality for those who developed ARFD was 35.7% and the 2-year survival was 18.8%.nnnCONCLUSIONnThe occurrence of ARFD after coronary intervention is rare (<1%) but is associated with high in-hospital mortality and poor long-term survival. Individual patient risk can be estimated from calculated CrCl, diabetic status, and expected contrast dose prior to a proposed coronary intervention.

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

Background. A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. Results. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P =0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. Conclusions. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation : Results at three years

Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), or cyclosporine (Neoral; CsA) + MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years. Results. The results at 3 years corroborate and extend the findings of the 2-year results. Patients with DGF treated with TAC+MMF experienced an increase in 3-year allograft survival compared with patients receiving CsA+MMF (84.1% vs. 49.9%, P =0.02). Patients randomized to either treatment arm containing TAC exhibited numerically superior kidney function when compared with CsA. During the 3 years, new-onset insulin dependence occurred in 6, 3, and 11 patients in the TAC+MMF, CsA+MMF, and TAC+AZA treatment arms, respectively. Furthermore, patients randomized to TAC+MMF received significantly lower doses of MMF as compared with those who received CsA+MMF. Conclusion. All three immunosuppressive regimens provided excellent safety and efficacy. However, the best results overall were achieved with TAC+MMF. The combination may provide particular benefit to kidney allograft recipients with DGF. In patients who experienced DGF, graft survival was better at 3 years in those patients receiving TAC in combination with either MMF or AZA as compared with the patients receiving CsA with MMF.

Relation between degree of weight loss after bariatric surgery and reduction in albuminuria and C-reactive protein.

BACKGROUNDnBariatric surgery achieves long-term weight loss in obese adults with amelioration of diabetes and hypertension. Improvement in albuminuria and high-sensitivity C-reactive protein (hs-CRP) has also been reported. We investigated, at a weight control center in a community hospital setting, the relation between degree of surgical weight loss and reduction in the cardiovascular risk markers, albuminuria and hs-CRP.nnnMETHODSnWe performed a retrospective study of 62 obese adults who had undergone Roux-en-Y gastric bypass surgery and had a median follow-up of 15 months.nnnRESULTSnThe baseline (preoperative) mean age was 46 years, 82% were women, 26 had a blood pressure of > or =140/90 mm Hg, and 25 had type 2 diabetes. During follow-up (postoperative), a decrease occurred in the body mass index (mean +/- standard deviation 49.2 +/- 8.7 kg/m(2) to 34.1 +/- 8.1 kg/m(2); P <.0001), excess body weight (mean +/- SD 76.1 +/- 23.6 kg to 34.9 +/- 21.7 kg; P <.0001), hemoglobin A1c (mean +/- SD 6.5% +/- 1.3% to 5.6% +/- 0.8%; P <.0001), systolic blood pressure (mean +/- SD 133.7 +/- 14.3 mm Hg to 112.9 +/- 14.6 mm Hg; P < .0001), urine albumin creatinine ratio (from a median of 8.0 mg/g [interquartile range 5.0-29.3] to a median of 6.0 mg/g [interquartile range 3.3-11.5]; P <.0001), and hs-CRP (mean +/- SD 11.2 +/- 9.8 mg/L to 4.7 +/- 5.9 mg/L; P <.0001). The study sample was divided into tertiles of the percentage of excess body weight loss; the mean percentage of excess body weight loss was -37.1% +/- 5.5% in the first tertile, -54.3% +/- 6.8% in the second tertile, and -75.8% +/- 10.9% in the third tertile. The median percentage of change in albuminuria was greatest (median -52.8%, interquartile range -79.1% to -17.5%) in the third tertile, intermediate (median -45.5%, interquartile range -72.4% to 0%) in the second tertile, and lowest (-42.6%, interquartile range -80.5% to 16.7%) in the first tertile (P = .953). The mean percentage of change in hs-CRP was greatest (-72.4% +/- 30.4%) in the third tertile, intermediate (-55.4% +/- 31.9%) in the second tertile, and lowest (-44.8% +/- 30.6%) in the first tertile (P = .037).nnnCONCLUSIONnThe results of our study have shown that obese adults experience a reduction in albuminuria and hs-CRP after bariatric surgery, with a greater reduction in hs-CRP observed with more surgical weight loss.

Severe Necrotizing Adenovirus Tubulointerstitial Nephritis in a Kidney Transplant Recipient

Adenoviruses (AdV) are emerging pathogens with a prevalence of 11% viruria and 6.5% viremia in kidney transplant recipients. Although AdV infection is common, interstitial nephritis (ADVIN) is rare with only 13 biopsy proven cases reported in the literature. We report a case of severe ADVIN with characteristic histological features that includes severe necrotizing granulomatous lesion with widespread tubular basement membrane rupture and hyperchromatic smudgy intranuclear inclusions in the tubular epithelial cells. The patient was asymptomatic at presentation, and the high AdV viral load (quantitative PCR>2,000,000 copies/mL in the urine and 646,642 copies/mL in the serum) confirmed the diagnosis. The patient showed excellent response to a combination of immunosuppression reduction, intravenous cidofovir, and immunoglobulin therapy resulting in complete resolution of infection and recovery of allograft function. Awareness of characteristic biopsy findings may help to clinch the diagnosis early which is essential since the disseminated infection is associated with high mortality of 18% in kidney transplant recipients. Cidofovir is considered the agent of choice for AdV infection in immunocompromised despite lack of randomized trials, and the addition of intravenous immunoglobulin may aid in resolution of infection while help prevention of rejection.

Renal Allograft Outcome in Recipients of Positive-Crossmatch Combined Liver-Kidney Transplantation

BACKGROUNDnSuccessful kidney transplantation despite positive crossmatch (+CXM) before transplantation is well recognized in combined liver-kidney transplant (CLKT) recipients. This is probably due to immunologic protection of the renal allograft (RA) conferred by the liver allograft. However, occurrences of antibody-mediated rejection and poor long-term RA outcome is also documented with +CXM CLKT recipients, suggesting that such immunologic protection may not be universal.nnnMETHODSnA total of 1,401 CLKT recipients with known status of pre-transplantation CXM were identified from the United Network for Organ Sharing registry from January 1, 1986, to December 31, 2006. Univariate analysis for significant differences in clinical variables and Kaplan-Meier estimate for patient and graft survivals were performed. The results were compared between positive and negative CXM groups.nnnRESULTSnPre-transplantation +CXM was seen in 17.3% (242/1401) of CLKT recipients studied. The demographic and clinical characteristics were similar between the groups, except for higher panel reactive antibody level and CXM positivity in female recipients. Outcome analysis showed higher RA rejection (19.3% vs 10.8%; P = .026) and increased hospital length of stay (37.3 ± 46.0 vs 28.8 ± 33.2 days; P = .028) in the +CXM group. RA survivals at 1, 3, and 5 years were 8%, 7%, and 6% lower in the +CXM group. The patient and liver allograft survivals were not different between the groups.nnnCONCLUSIONSnIn CLKT recipients with pre-transplantation +CXM, the immunologic protection of RA conferred by the liver allograft is less robust than previously perceived and may lead to higher rejection rate and poor RA outcome. This can be mitigated with routine pre-transplantation CXM.

Acute Tubular Injury Is an Important Component in Type I Acute Antibody-Mediated Rejection

BACKGROUNDnAcute tubular necrosis (ATN)-like changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of ATN-like injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1).nnnDESIGNnThe study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed.nnnRESULTSnGroup 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3).nnnCONCLUSIONnOur results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

Glomerulitis During Acute Cellular Rejection May Be a Surrogate Marker of Vasculitis in Renal Allografts—Better Index for Diagnosis of Vasculitis

BACKGROUNDnThe Banff criteria (from 2005 to 2009) use T cell-mediated rejection to indicate acute cellular rejection. Vasculitis in smaller arteries is an important diagnostic criterion for moderate and severe T cell-mediated rejection. The renal allograft endothelium is a significant target of inflammatory response-mediated tissue damage. Medium-size arteries (arcuate arteries) are mostly absent in routine allograft biopsies, so identification of vasculitis relies on its identification in small arteries (arterioles to interlobar arteries). Although inflammation in terminal vessels such as the glomerular capillaries has been previously recognized, their role in grading the rejection process is not well characterized. We therefore evaluated the expression of CD3-positive T lymphocytes and CD68-positive macrophages in glomeruli, small arteries, and arcuate arteries of nephrectomy specimens obtained from transplant and renal tumor patients.nnnMETHODSnThe study group included 21 renal explant subjects with nonreversible moderate to severe T cell-mediated rejection (IIa to III) and/or severe chronic changes. The control group comprised 17 individuals with nephrectomy for renal tumors. In each case, a large renal section from cortex to medulla was stained for CD3 and CD68 by immunohistochemical method. CD3-positive T lymphocytes and CD68-positive macrophages per balanced high-power field were counted in glomeruli, interlobar arteries, and arcuate arteries.nnnRESULTSnIn control kidney sections, neither CD3-positive T lymphocytes nor CD68-positive macrophages were noted in glomeruli, interlobar arteries, or arcuate arteries. In the study group, 15/21 showed diffuse C4d positivity. Also in the study group, positive CD3 and CD68 counts in glomeruli were significantly correlated to both interlobar and arcuate artery counts by linear regression analysis.nnnCONCLUSIONnWe conclude that in renal allograft biopsies, T lymphocytes and macrophages in the glomeruli not only represent a separate entity, transplant glomerulitis, but also may be a surrogate marker of vasculitis present in larger vascular beds. Comparable amounts of T cells and macrophages imply that acute cellular rejection may be a better terminology to reflect the true inflammatory status.

Primary Cilia Metaplasia in Renal Transplant Biopsies with Acute Tubular Injury

Abstract Primary cilia are hair-like organelles singly distributed along the apical surface of proximal and distal nephron tubules as mechanosensors. The goal of this study was to use electron microscopy to systemically evaluate cilia changes in acute tubular injury (ATI) from both transplant and native renal biopsies. Three groups of cases were included: control group 1—native biopsies without major changes in renal tubules; study group 2—native biopsies with prominent ATI; and study group 3—renal transplant biopsies with prominent ATI (delayed renal function group). Extensive search for ciliary structures along renal tubules was conducted in each case, focused on proximal tubular areas with injured (diminished) apical microvilli. Singly located cilia were found in 3/19 specimens in control group 1, 4/18 in group 2 (native ATI), and 6/24 in group 3 (transplant ATI). Importantly, there were clusters of cilia in proximal tubules with markedly diminished apical microvilli in 3/24 biopsies from 2 patients in group 3, but none from groups 1 and 2. The clusters of cilia ranged from 6 to 15 individual cilia along the apical surface with diminished apical microvilli. Under high magnifications, the cilia demonstrated 9 pairs of peripheral microtubules without a central pair of microtubules, consistent with primary cilia (9u2009+u20090) rather than motile cilia (9u2009+u20092). In summary, the authors found clusters of cilia in proximal tubules with remarkable apical microvillar injury in 3 renal transplant biopsies with ATI, implying a reactive, or repairing, process following tubular injury, thus they name this finding “cilia metaplasia.

Primary Nonfunction of Renal Allograft Secondary to Acute Oxalate Nephropathy

Primary nonfunction (PNF) accounts for 0.6 to 8% of renal allograft failure, and the focus on causes of PNF has changed from rejection to other causes. Calcium oxalate (CaOx) deposition is common in early allograft biopsies, and it contributes in moderate intensity to higher incidence of acute tubular necrosis and poor graft survival. A-49-year old male with ESRD secondary to polycystic kidney disease underwent extended criteria donor kidney transplantation. Posttransplant, patient developed delayed graft function (DGF), and the biopsy showed moderately intense CaOx deposition that persisted on subsequent biopsies for 16 weeks, eventually resulting in PNF. The serum oxalate level was 3 times more than normal at 85u2009μmol/L (normal <27u2009μmol/L). Allograft nephrectomy showed massive aggregates of CaOx crystal deposition in renal collecting system. In conclusion, acute oxalate nephropathy should be considered in the differential diagnosis of DGF since optimal management could change the outcome of the allograft.