Long‐term evolution,secular trends,and risk factors of renal dysfunction following cardiac transplantation

Recent reports suggest that individuals who underwent heart transplantation in the last decade have improved post‐transplant kidney function. The objectives of this retrospective study were to describe the incidence and to identify fixed and time‐dependent predictors of renal dysfunction in cardiac recipients transplanted over a 25‐year period (1983–2008). To illustrate temporal trends, patients (n = 306) were divided into five groups based on year of transplantation. The primary endpoint was the estimated glomerular filtration rate (eGFR) at year 1. Secondary endpoints were time to moderate (eGFR <60 ml/min/1.73 m²) and severe renal dysfunction (eGFR <30 ml/min/1.73 m²). Risk factor analyses relied on multivariable regression models. Kidney function was mildly impaired before transplant (median eGFR=61.0 ml/min/1.73 m²), improved at discharge (eGFR=72.3 ml/min/1.73 m²; P < 0.001), decreased considerably in the first year (eGFR = 54.7 ml/min/1.73 m²; P < 0.001), and deteriorated less rapidly thereafter. At year 1, 2004–2008 recipients exhibited a higher eGFR compared with all other patients (P < 0.001). Factors independently associated with eGFR at year 1 and with moderate and severe renal dysfunction included age, gender, pretransplant eGFR, blood pressure, glycemia, and use of prednisone (P < 0.05). In summary, kidney function worsens constantly up to two decades after cardiac transplantation, with the greatest decline occurring in the first year. Corticosteroid minimization and treatment of modifiable risk factors (hypertension, diabetes) may minimize renal deterioration.     

Experience with belatacept rescue therapy in kidney transplant recipients

In kidney transplant recipients with chronic graft dysfunction, long‐term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy‐nine kidney transplant recipients treated with CNI‐based or mTORi‐based maintenance immunosuppression who had CNI‐induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m², increasing to 34.0 ± 15.2 ml/min/1.73 m² at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m²) or high proteinuria (>500 mg/l) at conversion. The Kaplan–Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post‐transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi‐based immunosuppression because of biopsy‐confirmed CNI‐induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m² at baseline to 31.1 ± 11.9 ml/min/1.73 m² at 12 months (P = 0.018). Belatacept‐based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI‐ or mTORi‐induced toxicity.     

Pre-transplant histology does not improve prediction of 5-year kidney allograft outcomes above and beyond clinical parameters

Pre-implant kidney biopsy is used to determine suitability of marginal donor kidneys for transplantation. However, there is limited data examining the utility of pre-implant histology in predicting medium term graft outcome. This retrospective study examined kidney transplants over a 10-year period at a single center to determine if pre-implant histology can identify cases of eGFR ≤35?ml/min/1.73m² at 5 year follow up beyond a clinical predictive logistic regression model. We also compared outcomes of dual kidney transplants with standard single kidney transplants. Of 1195 transplants, 171 received a pre-implant kidney biopsy and 15 were dual transplants. There was no significant difference in graft and patient survival rates. Median eGFR was lower in recipients of biopsied kidneys compared with standard kidney transplants (44 vs. 54?ml/min/1.73m², p?2, p?=?.64). Glomerular sclerosis (p?=?.05) and Karpinski Score (p?=?.03) were significant predictors of eGFR at 5-years in multivariate analysis but did not improve discrimination of eGFR ≤35?ml/min/1.73m² at 5-years beyond a clinical prediction model comprising donor age, donor hypertension and terminal donor creatinine (C-statistic 0.67 vs. 0.66; p?=?.647). Pre-implant histology did not improve prediction of medium-term graft outcomes beyond clinical predictors alone. Allograft function of dual transplant kidneys was similar to standard transplants, suggesting that there is scope to increase utilization of kidneys considered marginal based on histology.     

Renal function following living, standard criteria deceased and expanded criteria deceased donor kidney transplantation: impact on graft failure and death

We examined United States Renal Data System (USRDS) data for adult kidney transplant recipients in 1995–2003 (n = 87 575) to investigate associations of 12‐month renal function with long‐term clinical outcomes. Estimated glomerular filtration rate (eGFR) was computed by the Modification of Diet in Renal Disease (MDRD) equation. Associations of eGFR at the first transplant anniversary with graft and patient‐survival in years 1–9 post‐transplant were evaluated by multivariate nonlinear regression with spline forms, adjusted for recipient, donor, and transplant factors. Regardless of donor type, the likelihood of graft failure and death increased significantly with lower eGFR. The impact of poor eGFR was more pronounced for graft failure than death. Relative effects were similar across donor types, but were strongest among living‐donor recipients. For example, compared with reference eGFR of 80 ml/min/1.73 m², 1‐year eGFR of 20 ml/min/1.73 m² was associated with adjusted hazards ratios for subsequent death‐censored graft failure of 9.2 in living, 8.9 in standard criteria deceased, and 5.9 in expanded criteria deceased‐donor recipients. First‐year renal function after kidney transplantation has strong, nonlinear associations with subsequent allograft and patient survival regardless of donor type. Post‐transplant eGFR may be a useful end‐point for discriminating benefits of care strategies that differentially affect renal function.     

A Higher Glomerular Filtration Rate Predicts Low Risk of Developing Chronic Kidney Disease in Living Kidney Donors

Background

The risk of developing chronic kidney disease (CKD) among living kidney donors (LKDs) is seldom included in evaluations of patients’ outcomes. Potential risk factors and new criteria for estimating the glomerular filtration rate (eGFR) indexed for body surface area (BSA) were investigated with a view to prevent the development of CKD in LKDs.

Methods

We conducted a retrospective study of LKDs from May 1983 to March 2011. The Mann–Whitney U test and χ² test were used to analyze the male versus female groups. Survival analysis was plotted as CKD-free survival and analyzed separately by different eGFR index classifications. The Cox regression model was used to identify potential risk factors for development of CKD.

Results

A total of 105 LKDs with a mean age of 46.3 ± 12.5 years had a mean eGFR indexed for BSA of 88.9 ± 21.5 ml/min per 1.73 m². After a mean duration of 5.4 ± 4.9 years’ follow-up, eGFR dropped to 61.4 ± 16.4 ml/min per 1.73 m² (p = 0.002). Median CKD-free survival was only 5.7 years. The difference between eGFR ≥ 80 ml/min per 1.73 m² and <80 ml/min per 1.73 m² was not statistically significant (p = 0.980). Multivariate Cox regression analysis showed that higher eGFR at donation (HR = 0.952, p = 0.0199) could be a protective factor. The receiver operating characteristic (ROC) curve for initial eGFR with best sensitivity of 52.78 % and specificity of 81.40 % was obtained with a cutoff value of 90.2 ml/min per 1.73 m² for preoperative eGFR. An eGFR of 90 ml/min per 1.73 m² yielded a significant survival curve (p = 0.0199) after 21 years of follow-up. Further classifications of eGFR >90 ml/min per 1.73 m² into 90–99 ml/min per 1.73 m², 100–109 ml/min per 1.73 m², and ≥110 ml/min per 1.73 m² were examined, but this survival curve was not statistically significant (p = 0.1247).

Conclusions

Living kidney donors will develop CKD after a long duration of follow-up if there is insufficiently high eGFR at donation. An eGFR above 90 ml/min per 1.73 m² before donation is the only factor that predicts prevention of CKD. Larger studies with longer duration of follow-up are necessary to clarify the clinical outcome of this postoperative CKD group, especially for patients with eGFR between 80 and 90 ml/min per 1.73 m².     

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m². In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m² higher eGFR at levels below 45 mL/min/1.73 m² was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m². In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.     

Fast GFR decline and progression to CKD among primary care patients with preserved GFR

Background

Fast glomerular filtration rate (GFR) decline is associated with adverse outcomes, but the associated risk factors among patients without chronic kidney disease (CKD) are not well defined.

Methods

From a primary care registry of 37,796, we identified 2219 (6%) adults with at least three estimated (e)GFR values and a baseline eGFR between 60 and 119 ml/min/1.73 m² during an observation period of 8 years. We defined fast GFR decline as > 5 ml/min/1.73 m² per year. The outcome measure was incident CKD (eGFR < 60 ml/min/1.73 m²). Clinical and demographic characteristics were compared using Chi-square and independent-samples t tests.

Results

Older age, African-American race, unmarried status, hypertension and type 2 diabetes were more common in both fast decliners and those who developed incident CKD (p < 0.0001 to < 0.05). Lower neighborhood socioeconomic status, current smoking and baseline eGFR 90–119 ml/min/1.73 m² were associated with fast decline (p < 0.01), while baseline eGFR 60–74 ml/min/1.73 m² with incident CKD (p < 0.05). In multivariate regression models, among fast decliners with mildly reduced baseline eGFR (60–89 ml/min/1.73 m²), older age was significantly associated with incident CKD [odds ratio (OR) 1.04; 95% CI 1.01–1.08], and among those with normal baseline eGFR (≥ 90–119 ml/min/1.73 m²), type 2 diabetes was significantly associated with incident CKD (OR 3.83; 95% CI 1.35–10.89).

Conclusions

Among primary care patients without CKD, GFR is checked infrequently. We have identified patients at high risk of progressive CKD, in whom we suggest a closer monitoring of renal function.

     

Renal function recovery after radical nephroureterectomy for upper tract urothelial carcinoma

Purpose

To understand the longitudinal renal function trends in patients undergoing radical nephroureterectomy (RNU) and identify clinicopathologic characteristics associated with estimated glomerular filtration rate (eGFR) recovery.

Methods

147 patients were available for analysis. Longitudinal eGFR trends were assessed by plotting each patient’s eGFR measurements over time. The patient population was dichotomized using eGFR < 60 ml/min/1.73 m² versus ≥ 60 ml/min/1.73 m². Cumulative incidence and competing risk regression analysis were used to estimate recovery of postoperative eGFR to the preoperative level and identify clinicopathologic characteristics associated with eGFR recovery.

Results

Median age was 68.7 years and median preoperative eGFR was 55.9 ml/min/1.73 m². 63.6% were male and 95.8% were white. The cumulative incidence of eGFR recovery was significantly higher in patients with baseline eGFR < 60 ml/min/1.73 m² compared to those with baseline eGFR ≥ 60 ml/min/1.73 m² (p = 0.01), with recovery rates at 2 years of 56.6% vs. 27.7%, respectively. Multivariable analysis revealed that preoperative hydronephrosis (HR 1.80) and preoperative eGFR < 60 ml/min/1.73 m² (HR 1.87) were associated with increased chance of eGFR recovery.

Conclusion

Over half of patients with preoperative eGFR < 60 ml/min/1.73 m² achieved eGFR recovery within the first 3 years after RNU, and hydronephrosis was a significant predictor of recovery. These findings should be considered when counseling patients regarding chronic kidney disease progression after RNU and timing of perioperative chemotherapy for high risk tumors.

     

Renal function in type 1 diabetics one year after successful pancreas transplantation

Chatzizacharias NA, Vaidya A, Sinha S, Smith R, Jones G, Sharples E, Friend PJ. Renal function in type 1 diabetics one year after successful pancreas transplantation.
Clin Transplant 2011: 25: E509–E515. © 2011 John Wiley & Sons A/S. Abstract: The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single‐unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty‐nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post‐transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m²) and low (≤45 mL/min/1.73 m²) pre‐transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post‐transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post‐transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre‐existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.     

Pre‐ and postdonation kidney function in donors of a kidney paired donation with unique criteria for donor glomerular filtration rate – a longitudinal cohort analysis

Baseline predonation estimated GFR (eGFR) appears to predict the risk of postdonation chronic kidney disease in live donors. New KIDGO guidelines recommend an eGFR ≥90 ml/min/1.73 m² as an acceptable level of glomerular filtration rate (GFR) for kidney donation. In the Australian Paired Kidney Exchange (AKX) program, all donors with a raw measured GFR (mGFR) ≥80 ml/min are deemed suitable for donation, but the significance of this selection indicator is unclear. We analysed the first 129 live donors in the AKX program with at least 1‐year follow‐up linking records in the AKX database and ANZDATA. There were 73 male and 56 female donors; mean (±SD) age was 53 ± 11 years. Predonation eGFR was 94 ± 13 ml/min/1.73 m², mGFR 99 ± 17 ml/min/1.73 m² and raw mGFR 108 ± 18 ml/min. Baseline eGFR was <80 ml/min/1.73 m² in 19 donors, and <90 ml/min/1.73 m² in 42 donors. At 1 year postdonation eGFR was 68 ± 15 ml/min/1.73 m² and the predicted eGFR at 30 years postdonation was on average 50 (29–83) ml/min/1.73 m². The hypothetical mean age at end‐stage kidney disease was estimated to be 145 (95% CI 120–263) years. Over 30% of AKX live donors would have been excluded from donation using KDIGO guidelines. Using AKX donor guidelines, the majority of donors with predicted eGFR <30 ml/min/1.73 m² 30‐year postdonation were aged ≥50 years. Long‐term outcome data on AKX donors with low eGFR will need careful monitoring.     

Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism

Background

Corticosteroids have been widely used in patients with cholesterol crystal embolism (CCE) and low-density lipoprotein apheresis (LDL-A) was reported to reduce the risk of end-stage renal disease in patients with CCE. This study was designed to evaluate the renoprotective effects of LDL-A in combination with corticosteroids in patients with CCE.

Methods

Thirty-five patients with CCE who, between 2008 and 2013, had shown renal deterioration after vascular interventions were retrospectively evaluated. All patients received corticosteroids; of these, 24 also received LDL-A and 11 did not, designated LDL-A and control groups, respectively. Differences in eGFR (ΔeGFR), 3 months and 1 year after CCE diagnosis, were compared in the two groups.

Results

The median estimated glomerular filtration rate (eGFR) in all patients was 38.9 [interquartile range (IQR) 31.9–49.4] ml/min/1.73 m² at baseline (before vascular intervention). At diagnosis, it was 14.4 (IQR 11.3–21.8) ml/min/1.73 m². The initial corticosteroid dose was 0.34 ± 0.10 mg/kg/day. The mean number of LDL-A treatment sessions in the LDL-A group was 4.3 ± 1.8. eGFR was increased significantly after LDL-A treatments, from 15.0 (IQR 12.3–20.1) to 19.6 (IQR 14.3–23.6) ml/min/1.73 m² (P < 0.05). ΔeGFR tended to be higher in the LDL-A than in the control group at 3 months [median 6.5 (IQR 5.1–9.3) vs. 2.6 (IQR ?0.6 to 6.3) ml/min/1.73 m², P = 0.095] and was significantly higher at 1 year [median 7.5 (IQR 5.4–8.7) vs. 2.2 (IQR ?3.8 to 5.1) ml/min/1.73 m², P = 0.019].

Conclusions

LDL-A plus corticosteroids may restore deteriorated renal function better than corticosteroids alone in patients with CCE.

     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Delayed Recovery of Renal Function After Donor Nephrectomy

Background

Many living kidney donors are still at risk of chronic kidney disease (CKD) 1 year after nephrectomy. Although some donors still experience poor renal function, many exhibit delayed recovery of renal function afterwards. We studied the factors related to delayed recovery of renal function in patients with CKD at 1 year after nephrectomy.

Progression of chronic renal failure in children with dysplastic kidneys

The aim of this study is to describe progression of chronic renal failure (CRF) in children with renal malformations and to study factors influencing this progression. We reviewed retrospectively 176 children with CRF secondary to renal dysplasia, reflux nephropathy or renal obstruction with at least 5 years of follow-up. Serum creatinine was recorded at least every third month, and an estimated glomerular filtration rate (eGFR) was calculated. Number of febrile urinary tract infections (UTI), blood pressure, albuminuria (UaUc), and number of functioning kidneys was also recorded. We found that the development of renal function could be separated into three time periods: (1) During the first years of life, 82% of the children showed early improvement of their kidney function, which lasted until a median age of 3.2 years (median improvement 6.3 ml/year). (2) From the age of 3.2 years until 11.4 years, 52.5% of the studied children showed a stable kidney function, whereas in 47.5%, kidney function immediately started to deteriorate. (3) Around puberty, 42.9% started deterioration in kidney function, whereas 57.1% even after puberty showed a stable function. Patients with UaUc >200 mg/mmol deteriorated faster (−6.5 ml/min per 1.73 m² per year compared with −1.5 ml/min per 1.73 m² per year) in those with UaUc <50 mg/mmol. Children with more than two febrile UTIs, hypertension or an eGFR at onset of less than 40 ml/min per 1.73 m² deteriorated faster than the others. Most children experienced early improvement of kidney function. The further prognosis, early or late deterioration of kidney function or stable function during the whole follow-up, was related to albuminuria, number of febrile UTIs, eGFR at onset of deterioration, hypertension and puberty.     

99Tcm-DTPA肾动态显像评估单侧根治性肾切除术后早期患者肾功能

目的 观察⁹⁹Tc^m-二亚乙基三胺五乙酸（DTPA）肾动态显像评估单侧根治性肾切除术后早期患者肾功能的价值。方法 回顾性分析158例接受根治性肾切除术的单侧肾实质肿瘤患者资料及术前经肾动态显像所获肾小球滤过率（GFR）结果,计算估算GFR （eGFR）,并以eGFR 60、90 ml/（min·1.73 m²）为临界值将患者分为3组;评价各组临床资料、肾功能指标与术后3个月eGFR的关系,并以线性回归分析影响术后早期肾功能的独立因素。结果 术前eGFR<60 ml/（min·1.73 m²）患者术后早期肾功能与术前eGFR及对侧GFR均相关（P均<0.05）;对侧GFR为术后早期肾功能的独立影响因素（调整R²=0.910,P<0.001）。术前60 ml/（min·1.73 m²）≤ eGFR<90 ml/（min·1.73 m²）时,术后早期肾功能与患者年龄、高血压病史及术前对侧GFR均相关（P均<0.05）,其中术前对侧GFR为独立影响因素（调整R²=0.463,P<0.001）;术前eGFR ≥ 90 ml/（min·1.73 m²）时,术后早期肾功能与患者年龄、肿瘤性质、术前eGFR、对侧GFR及患侧GFR均相关（P均<0.05）,其中患者年龄、术前eGFR及对侧GFR为独立影响因素（调整R²=0.486,P<0.001）。结论 术前⁹⁹Tc^m-DTPA肾动态显像可用于评估单侧根治性肾切除术后早期患者肾功能。     

Utility of the Japanese GFR estimation equation for evaluating potential donor kidney function

Background

In Japan, the number of living kidney transplantations has increased each year, and an accurate evaluation of renal function must be conducted before donation to minimize the risk to donors. Recently, the Japanese Society of Nephrology issued a new equation for estimating glomerular filtration rate (eGFR) in Japanese people. This study compared the accuracy of eGFR and creatinine clearance (Ccr) values with that of inulin clearance (Cin) for assessing renal function in kidney donors.

Methods

Clinical data were analyzed for 85 potential living kidney donors who had undergone routine measured GFR (mGFR) and Ccr measurements from October 2006 to November 2008 at a single center. Inulin clearance, representing the mGFR, was determined by standard method. The eGFR was calculated as: eGFR = 194 × Scr^?1.094 × Age^?0.287 (for females, ×0.739).

Results

Mean mGFR was 96.1 ± 14.7 (range 67.8–126.8); mean eGFR, 72.6 ± 12.7 (range 50.1–107.1); and mean Ccr, 117.3 ± 22.4 (range 35.1–170.1), in units of ml/min/1.73 m² for each. Relative to mGFR, the correlation coefficient for Ccr was 0.496, and the mean difference between the two values was 21.1 ml/min/1.73 m² (23.2%), with a root-mean square error (RMSE) of 19.6. The correlation coefficient between eGFR and mGFR was 0.502, and the mean difference between the two values was ?23.5 (23.7%), with a RMSE of 11.0. Bland–Altman plots showed that Ccr overestimated mGFR in 90.6% of cases, whereas eGFR underestimated mGFR in 95.3% of cases.

Conclusion

Ccr and eGFR values did not accurately estimate mGFR in Japanese living kidney donors.     

Kidney outcomes and prognostic factors of myeloma associated acute kidney injury in the contemporary era

Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma-associated acute kidney injury (M-AKI) in the contemporary era of anti-plasma cell therapy. Patients who received anti-myeloma therapy with M-AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records. Diagnosis of MCN was either biopsy confirmed (BC) or clinically suspected (CS), the latter defined as acute kidney injury with reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² and involved serum free light chains (iSFLC) >500 mg/L at diagnosis. Twenty-six patients with M-AKI were identified (BC: n = 13, CS: n = 13). Median eGFR at diagnosis was 12 (interquartile range 6–20) mL/min/1.73 m². All six dialysis-requiring patients achieved dialysis independence after 71 (43–208) days. The best-achieved eGFR was 47 (32–67) mL/min/1.73 m² after 120 (63–167) days post-treatment, which was maintained at 47 (33–66) mL/min/1.73 m² 12 months post-treatment. Patients with best-achieved eGFR above the median were more likely to have achieved an iSFLC of <20 mg/L (above median group 62% versus below median group 0%; p < .001) and lower best post-treatment iSFLC (20 (12–90) versus 67 (29–146) mg/L; p < .05). Best-achieved iSFLC was a prognostic factor for superior eGFR following treatment for M-AKI. Despite low eGFR at diagnosis, contemporary anti-myeloma therapy can achieve significant recovery of kidney function.     

The correlation between preoperative renal scintigraphy and postoperative renal function in upper urinary tract urothelial carcinoma patients following radical nephroureterectomy

ObjectiveTo predict the renal function after nephroureterectomy (NUR) for upper urinary tract urothelial cancer (UTUC) based on preoperative technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) renal scintigraphy.Subjects and methodsWe retrospectively reviewed 238 patients who originally underwent nephroureterectomy for UTUC between 2007 and 2010. Of these patients, 129 underwent MAG3 renal scintigraphy before unilateral NUR. Serum creatinine was measured in all of the patients before surgery, and renal function was monitored for one year after surgery. Preoperative and postoperative eGFRs were compared and analyzed based on the preoperative MAG3 renal scintigraphy.ResultsA total of 129 patients, including 62 men (48%) and 67 women (52%) with an average age at surgery of 69.0 years (range from 48 to 87) were included in this study. The mean preoperative creatinine level was 1.42 mg/dL, and the baseline eGFR was 54.76 ml/min/1.73 m². One year after NUR, the mean creatinine level was 1.89 mg/dL, and the eGFR was 44.44 ml/min/1.73 m², a mean decrease of 18.73%. The preoperative effective renal plasma flow (ERPF) of the operated kidney was 91.65 ml/min/1.73 m², and that of the remaining kidney 158.30 ml/ min/1.73 m². The average preoperative ERPF of the resected kidney accounted for 34% of total preoperative ERPF, which was statistically significant in its relation to the decrease in eGFR. The decrease in eGFR ratio was also significantly correlated with the calculated decrease in ERPF ratio (R² = 0.279, p < 0.001). The predictive equation of renal function one year after NUR was established as following: eGFR decreased ratio = –0.80 × predictive ERPF decreased ratio +0.72.ConclusionWe developed an equation to predict postnephroureterectomy 1 year eGFR before surgery based on preoperative MAG3 renal scintigraphy results and preoperative eGFR. The equation could be more accurate in the situation if the diseased kidney is not hydronephrotic.     

Galectin-3, Renal Function,and Clinical Outcomes: Results from the LURIC and 4D Studies

Galectin-3 has been linked to incident renal disease, experimental renal fibrosis, and nephropathy. However, the association among galectin-3, renal function, and adverse outcomes has not been described. We studied this association in two large cohorts of patients over a broad range of renal function. We measured galectin-3 concentrations in baseline samples from the German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2 diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2579 patients with coronary angiograms). Patients were stratified into three groups: eGFR of ≥90 ml/min per 1.73 m², 60–89 ml/min per 1.73 m², and <60 ml/min per 1.73 m². We correlated galectin-3 concentrations with demographic, clinical, and biochemical parameters. The association of galectin-3 with clinical end points was assessed by Cox proportional hazards regression within 10 years (LURIC) or 4 years (4D) of follow-up. Mean±SD galectin-3 concentrations were 12.8±4.0 ng/ml (eGFR≥90 ml/min per 1.73 m²), 15.6±5.4 ng/ml (eGFR 60–89 ml/min per 1.73 m²), 23.1±9.9 ng/ml (eGFR<60 ml/min per 1.73 m²), and 54.1±19.6 ng/ml (dialysis patients of the 4D study). Galectin-3 concentration was significantly associated with clinical end points in participants with impaired kidney function, but not in participants with normal kidney function. Per SD increase in log-transformed galectin-3 concentration, the risks of all-cause mortality, cardiovascular mortality, and fatal infection increased significantly. In dialysis patients, galectin-3 was associated with the combined end point of cardiovascular events. In conclusion, galectin-3 concentrations increased with progressive renal impairment and independently associated with cardiovascular end points, infections, and all-cause death in patients with impaired renal function.     

Early post‐transplant conversion from tacrolimus to belatacept for prolonged delayed graft function improves renal function in kidney transplant recipients

Prolonged delayed graft function (DGF) in kidney transplant recipients imparts a risk of poor allograft function; tacrolimus may be detrimental in this setting. We conducted a retrospective single center analysis of the first 20 patients converted to belatacept for prolonged DGF as part of a clinical protocol as a novel treatment strategy to treat prolonged DGF. Prior to conversion, patients underwent an allograft biopsy to rule out rejection and confirm tubular injury. The primary outcome was the estimated glomerular filtration rate (eGFR) at 12 months post‐transplant; secondary outcome was the change in eGFR 30 days post‐belatacept conversion. At 1 year post‐transplant, the mean eGFR was 54.2 (SD 19.2) mL/min/1.73 m². The mean eGFR on the day of belatacept conversion was 16 (SD 12.7) mL/min/1.73 m² and rose to 43.1 (SD 15.8) mL/min/1.73 m² 30 days post‐conversion (P<.0001). The acute rejection rate was 20% with 100% patient survival at 12 months post‐transplant. There was one graft loss in the setting of an invasive Aspergillus infection that resulted in withdrawal of immunosuppression and transplant nephrectomy. Belatacept conversion for prolonged DGF is a novel treatment strategy that resulted in an improvement in eGFR. Additional follow‐up is warranted to confirm the long‐term benefits of this strategy.