Obesity and the kidney: Why is the kidney at risk?

Two recent studies may help to account for the increase in risk of renal injury associated with obesity. One study pointed to a role for renin-system activation. In the other study, the pattern of renal hemodynamics was compatible with a renin mechanism.     

Why do preemptive kidney transplant recipients have an allograft survival advantage?

BACKGROUND: Preemptive kidney transplantation is associated with an allograft survival advantage and is promoted in part because of this association. The basis for the allograft survival advantage in preemptive recipients is unclear. Possibilities include a lead time bias due to the earlier transplantation of patients with preserved native kidney function, less rapid loss of kidney function after transplantation, or the longer patient survival of preemptive recipients. METHODS: We compared the glomerular filtration rate (GFR) six months after transplantation and the subsequent rate of loss of kidney function as defined by the annualized change in GFR (mL/min/1.73 m2/year) in 5,966 preemptive and 34,997 non-preemptive recipients. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Multiple regression was used to determine the independent effect of preemptive transplantation upon the annualized change in GFR. RESULTS: The mean GFR six months after transplantation was similar among preemptive (49.5+/-15.7 mL/min/1.73 m2) and non-preemptive (49.2+/-14.7 mL/min/1.73 m2) recipients (P=0.37). In multivariate analysis, preemptive recipients had a slower decline in GFR (0.28 mL/min/year/1.73 m2; 95% confidence interval 0.11, 0.46; P=0.002). However, this difference was of modest clinical significance and would not explain the allograft survival advantage of preemptive transplantation. CONCLUSIONS: Neither the preservation of native kidney function nor differences in the rate of loss of kidney function explain the superior allograft survival of preemptive recipients. By exclusion, the allograft survival advantage associated with preemptive transplantation may be due to the longer survival of preemptive recipients.     

Why do some diabetic patients on the kidney transplant waiting list not receive a transplant?

The waiting list (WL) history of 405 diabetic patients placed on the kidney transplantation WL for the years 1993–2000 was examined. By 31 December 2000, 295 (73 %) patients had received a transplant. Of the remaining 110 patients 53 (13 %) were still on the WL; 27 of these were temporarily withdrawn, i.e. non-active, 46 others (11 %) had died and 11 (3 %) had been permanently removed. Patient follow-up continued until the end of 2002. Although the mean total time on the WL of the non-transplanted was twice that of the transplanted patients there were no significant differences in the mean active times on the WL. The mean cumulative withdrawal time of the transplanted and those on the active WL was less than 10 % of their total time on the list, but for the patients who had died or were withdrawn on 31 December 2000 it exceeded 50 %, usually because of diabetic complications. The 5-year survival of the transplanted patients was greatly superior to that of the non-transplanted, as expected. However, the better survival of the transplanted patients is not necessarily proof of a better treatment modality but rather a consequence of the exclusion from transplantation of patients suffering from diabetic complications. It is not justified to compare the survival of transplantable and non-transplantable WL patients.     

Observational study of risk factors associated with clinical outcome among elderly kidney transplant recipients in Sweden – a decade of follow-up

Kidney transplantation (Ktx) in elderly has become increasingly accepted worldwide despite their higher burden of comorbidities. We investigated important risk factors affecting long-term patient and graft survival. We included all (n = 747) Ktx patients >60 years from 2000 to 2012 in Sweden. Patients were age-stratified, 60–64, 65–69 and >70 years. Follow-up time was up to 10 years (median 7.9 years, 75% percentile >10 years). Primary outcome was 10-year patient survival in age-stratified groups. Secondary outcomes were 5-year patient and graft survival in age-stratified groups and the impact of risk factors including Charlson comorbidity index (CCI) on patient and graft survival. Mortality was higher in patients >70 years, after 10 years (HR 1.94; 95% CI 1.24–3.04; P = 0.004). Males had a higher 10-year risk of death (HR 1.39; CI 95% 1.04–1.86; P = 0.024). Five-year patient survival did not differ between age groups. In multivariate Cox analysis (n = 500), hazard ratio for 10-year mortality was 4.6 in patients with CCI ≥7 vs. <4 (95% CI 2.42–8.62; P = 0.0001). Higher CCI identified ESKD patients with 4.6 times higher risk of death after Ktx. We suggest that this index should be used as a part of the preoperative evaluation in elderly.     

Cardiovascular risk factors in chronic kidney disease: does phosphate qualify?

Risk factors for disease states are rigorously defined. This analysis considers the definition of a risk factor as applied to the question of whether the serum phosphorus level is a risk factor for cardiovascular disease. Observational studies strongly suggest that phosphorus is associated with cardiovascular risk, and definitive prospective animal studies are supportive. A plausible mechanism of action has been discovered demonstrating that phosphorus stimulates osteoblastic transition of cells in the neointima of atherosclerotic plaques, which, if prevented, blocks vascular calcification. However, prospective studies demonstrating that modulation of the putative risk factor affects clinical outcomes are lacking, and phosphorus, as yet, does not qualify as a cardiovascular risk factor. This is a clarion call for additional research.     

Bilirubin,a new therapeutic for kidney transplant?

In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.     

Liver alone or simultaneous liver–kidney transplant? Pretransplant chronic kidney disease and post‐transplant outcome – a retrospective study

The new Organ Procurement and Transplant Network/United Organ Sharing Network (OPTN/UNOS) simultaneous liver–kidney transplant (SLK) policy has been implemented. The aim of this study was to review liver transplant outcomes utilizing the new SLK policy. Liver transplant alone (LTA) and SLK patients between 2009 and 2015 were reviewed. Graft survival and post‐transplant kidney function were investigated among LTA patients meeting the chronic kidney disease (CKD) criteria of the new policy (LTA‐CKD group). To validate our findings, we reviewed and applied our analysis to the OPTN/UNOS registry. A total of 535 patients were eligible from our series. The LTA‐CKD group (n = 27) showed worse 1‐year graft survival, compared with the SLK group (n = 44), but not significant (81% vs. 93%, P = 0.15). The LTA‐CKD group significantly increased a risk of post‐transplant dialysis (odds ratio = 5.59 [95% CI = 1.27–24.7], P = 0.02 [Ref. normal kidney function]). Post‐transplant dialysis was an independent risk factor for graft loss (hazard ratio = 7.25, 95% CI = 3.3–15.91, P < 0.001 [Ref. SLK]). In the validation analysis based on the OPTN/UNOS registry, the hazard of 1‐year‐graft loss in the LTA‐CKD group (n = 751) was 34.8% higher than the SLK group (n = 2856) (hazard ratio = 1.348, 95% CI = 1.157–1.572, P < 0.001). Indicating SLK for patients who meet the CKD criteria may significantly improve transplant outcomes.     

Cytomegalovirus infection in kidney transplant patients: Prevalence,risk factors,and impact on outcome – A local multicentre experience

BackgroundCMV infection prevalence in kidney transplant recipients (KTR) is reported to be high in the literature, reaching rates of over 80%.ObjectivesThe primary endpoints were the evaluation of the prevalence, the risks factors, and the effects of CMV infection on graft function and survival, as well as patient survival at three years after kidney transplantation.Material and methodsWe retrospectively reviewed the medical records of 288 kidney transplant patients operated in three Lebanese transplant centers between 1998 and 2017 with three years of follow-up. The patients were divided into two groups: those free of any CMV infection (271 patients (94%); Group I) and those who suffered from CMV infection (17 patients (6%); Group II).ResultsBaseline demographics of the two groups were similar, including recipient and donor gender and age, cause of renal disease, recipient body mass index, pre-transplant fasting blood sugar and dialysis duration, HLA matching between donor and recipient, degree of sensitization in the recipient, type of CMV prophylaxis, maintenance immunosuppression and immunological characteristics. The prevalence of CMV infection is 5.9% among KTR. There were significant differences between the two groups concerning the type of induction therapy and the duration of anti-CMV prophylaxis. The rate of infected patients and infectious episodes were significantly higher in Group II. At 3-years, graft function and survival, patient survival, and the rate of new-onset diabetes were similar between the two groups.ConclusionThe present study is the first to explore the incidence and risk factors of CMV in kidney transplant patients in Lebanon. Comprehensive nationwide studies are therefore necessary to determine the epidemiology and risk factors of CMV infection after kidney transplantation in Lebanon.     

Northern Australian kidney transplant unit: A viable option?

AIMS: Kidney transplant units in Australia are confined to large hospitals in major metropolitan areas, yet this may limit access and diminish outcomes in people who do not live in these large centres. The authors examined the viability of a kidney transplant unit located in northern Australia (NA), with particular emphasis on recipient outcomes and the number of donors. METHODS: 'Northern Australia' was arbitrarily defined as 'north of the tropic of Capricorn' for Queensland and Western Australia and included the entire Northern Territory. Data on donors and transplant recipients were provided by ANZDATA and ANZOD registries, identified by postcode. RESULTS: Between 1998 and 2004 in NA there were 163 deceased donor kidneys and 97.5% of available organs were transplanted. There were no Aboriginal/Torres Strait Islander (ATSI) donors from NA. Recipients from NA in this time included 55 patients receiving living grafts and 156 receiving deceased donor grafts, of whom 36% were ATSI, making up half of the total ATSI transplanted in Australia during this time period. Compared with the rest of Australia, NA recipients were older, waited longer on dialysis, had longer ischaemic times and a greater number of human leucocyte antigen mismatches, and were more likely to be diabetic and obese. Despite the longer cold ischaemic time in NA recipients, no difference in immediate graft function was seen. ATSI recipients in NA, when compared with their southern Australian counterparts, had poorer patient survival (HR=3.19, 95% CI 1.44-7.08, P<0.001), but equivalent graft survival (HR=1.67, 95% CI 0.95-2.95, P=not significant) on multivariate analysis. Key factors that would influence feasibility of a Northern Australian transplant unit include adequate staffing, and support services in addition to currently available resources. CONCLUSION: Current donor numbers in NA are adequate for past recipients of kidney transplant, but may not cover future needs without a significant increase in donor rate. A transplant unit situated in northern Australian would require significant resources to ensure long-term viability and its effect on outcomes is uncertain.     

Does graft mass impact on pediatric kidney transplant outcomes?

Background

The aim of this study is to assess the evolution of renal size and function in pediatric transplant patients according to the graft mass/recipient size ratio.

Methods

Fifty pediatric renal transplant recipients were followed over 2 years. Grafts were weighed, and three different graft mass/m² ratios were determined: (1) low graft mass (58 g/m², range?31–57 g/m²), (2) median (142 g/m², range?59–141 g/m²) and high (267 g/m², range?143–353 g/m²). Patients underwent repeated ultrasound Doppler scans and repeated measurements of estimated glomerular filtration rate (eGFR; 1 week and 1, 6, 12 and 24 months), urinary retinol-binding protein (RBP) and proteinuria (1 week and 6, 12 and 24 months).

Results

The volume of renal tissue increased by 12?±?5.6 cm³ at 24 months (p?=?0.035) in the low graft mass and decreased by ?14?±?7 cm³ (p?=?0.046) in the high graft mass. The eGFR increased when either low (30?±?5 ml/min/1.73 m², p?<?0.001) or median (19?±?4 ml/min/1.73 m², p?<?0.001) graft mass was transplanted but remained stable when high graft mass was transplanted. The resistive index (RI) presented a significant decrease throughout early follow-up in the transplants involving low and median graft mass, whereas a slight rise was observed in those involving high graft mass. A significant difference was apparent 6 months post-transplant. Transplants of low and median graft mass were associated with an initial higher urinary RBP. No significant differences in proteinuria were detected.

Conclusions

Small kidneys undergo increases in volume and function without escalation of either proteinuria or urinary RBP, characterizing an adequate adaptation to the recipient. Children receiving larger kidneys present a reduction in volume, stable GFR and higher RI at 6 months.     

Prehabilitation for kidney transplant candidates: Is it time?

Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and healthcare utilization after kidney transplantation. Efforts to intervene with post‐transplant physical therapy have been met with limited success, in large part due to high study dropout. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation.     

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Abstract Non‐melanoma skin cancer is frequent in organ transplant recipients. The risk of post‐transplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8‐times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.     

Biomarkers and risk factors for sepsis in stage 5 chronic kidney disease: a retrospective case–control study

International Urology and Nephrology - To assess the predictive value of procalcitonin (PCT) in the risk of sepsis in patients with stage 5 chronic kidney disease (CKD). A total of 373 inpatients...     

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.     

Does pretransplant obesity affect the outcome in kidney transplant recipients?

The effect of obesity on renal transplant outcome remains unclear due to conflicting published studies. The purpose of this study was to assess whether obesity affects the outcome in renal transplant patients. METHODS: We retrospectively analyzed 33 obese (BMI >30; mean = 34.1 +/- 3.68; group I) and 35 nonobese (BMI < or = 30; mean = 23.6 +/- 3.18; group II) renal transplants performed at our center between March 1999 to December 2002. These two groups were well matched with respect to age, sex, donor source, hypertension, diabetes, ischemic heart disease, hyperlipidemia, native kidney disease (PCKD, 6 vs 4; diabetic, 5 vs 4; glomerulonephritis, 6 vs 7; FSGS, 2 vs 2 and IgA, 2 vs 7), HLA mismatch and immunosuppressants medications (Neoral, 21 vs 25; tacrolimus, 11 vs 10; Cellcept, 28 vs 31; Prednisone, 33 vs 35; ATG, 7 vs 8; Basiliximab, 14 vs 13 and Rapamycin, 5 vs 2, groups I and II, respectively). Follow-up was from 7 months to 4.4 years. RESULTS: Significant differences were noted in operating time, wound infection, perinephric hematoma, lymphocele, and number of hospital days. There were no significant differences between the two groups in the incidence of wound dehiscence, deep vein thrombosis, pulmonary embolism, atelectasis, urine leak, delayed graft function, acute rejection rate, and the following posttransplant variables: diabetes mellitus, myocardial infarction, hyperlipidemia, hypertension, and incisional hernia. We conclude that obesity significantly increases operating time, wound complications, and hospitalizations.