Nephrology Dialysis Transplantation最新文献

Background: We investigated the long-term effect of COVID-19 on estimated glomerular filtration rate (eGFR) trajectory and the association with progression to kidney failure in patients with CKD.

Methods: Patients living with non-dialysis-dependent CKD from British Columbia, Canada infected with COVID-19 (cases) were matched 1:2 to non-COVID-19-infected controls on variables including pre-COVID-19 annual rate of eGFR decline. Patients were followed from 90 days from the date of COVID-19 diagnosis. The Cox proportional hazard model was used for the primary outcome of kidney failure, defined as a composite of eGFR reaching <15 ml/min/1.73 m2, initiation of maintenance dialysis or kidney transplantation. A linear mixed regression model was used to calculate the annual rate of change in eGFR.

Results: The study included 802 patients: 268 cases and 534 controls. The median age was 70 years and 54% were male. Over ≈3 years of follow-up, the risk of developing kidney failure did not differ significantly between cases and controls. The annual rate of eGFR decline was 2.05 ml/min/1.73 m2 among cases versus 1.35 ml/min/1.73 m2 among controls, representing a rate difference of 0.71 ml/min/1.73 m2 (P = .02).

Conclusion: In patients with non-dialysis-dependent CKD who survived at least 90 days without requiring dialysis, COVID-19 was not associated with an increased long-term risk of kidney failure over 3 years but was associated with a greater annual decline in eGFR. Future research with longer follow-up is required to examine if this difference persists and leads to increased risk for kidney failure.

Background and hypothesis: Psoriasis is a common immune-mediated skin disorder with additional manifestations due to systemic inflammation. Patients with psoriasis have an increased risk of end-stage renal disease (ESRD) requiring either dialysis or renal transplant; however, the relationship between psoriasis and renal allograft failure has not been established.

Methods: We conducted a retrospective cohort study using the United States Renal Data System to analyze the association between psoriasis and graft failure (occurring more than 2 weeks after the transplant). We compared transplant failure rates in ESRD patients with a psoriasis diagnosis prior to the initial transplant versus transplanted ESRD patients without a psoriasis diagnosis. From 2004 to 2019, a total of 151 272 renal transplant patients aged 18-100 and meeting exclusion and inclusion criteria were identified; in this cohort, 1105 ESRD patients had International Classification of Diseases (ICD)-9 and -10 claim codes for psoriasis prior to their renal transplant.

Results: Logistic regression modeling was used to examine possible confounders of psoriasis on graft failure. Kaplan-Meier estimates indicated that renal transplant patients with psoriasis had reduced graft survival over time compared with those without psoriasis. In addition, Cox proportional hazard analysis, controlling for demographics and clinical risk factors, showed a significantly increased hazard ratio for renal allograft failure for patients with a diagnosis of psoriasis.

Conclusions: The systemic inflammation and immune-mediated pathophysiology underlying psoriasis could underlie the association between psoriasis and the increased risk of renal transplant failure.

Background: Primary hyperoxaluria (PH) is a rare disorder with significant morbidity and mortality if left untreated. Given the rarity, global inequities in diagnostics and treatment are expected. Recently introduced RNA interference therapeutics (RNAi) have dramatically changed the outcome for PH patients, potentially disproportionately affecting low-resource regions. Understanding these disparities is crucial for implementing measures to ensure equitable healthcare access for PH patients worldwide. This study aims to evaluate the current global health situation for PH patients upon the introduction of targeted therapeutics.

Methods: An international cross-sectional questionnaire study was conducted among healthcare providers involved in PH care. Responses were gathered between March 2023 and April 2024 and distributed by e-mail via various international nephrology networks. Meta-analysis (mixed random effects model with inverse-variance weighting) was used to analyze data and adjust for subgroup differences.

Results: We gathered 136 responses from 57 countries, representing all World Bank regions. Overall access to genetic analysis diagnostics was 82% (confidence interval 77%-91%) and to urinary oxalate measurement 97% (93%-100%). Significant differences (P < .05) between low- and high-income countries were found for most diagnostics including genetic testing, plasma oxalate, plasma and urinary glycolate. Conservative therapies (e.g. pyridoxine and alkalinizing agents) were highly available globally (98% and 95%), but significant differences in access to peritoneal dialysis, and kidney and liver transplantation were reported (P < .05). Access to the RNAi therapeutic lumasiran was limited to high- and middle-income countries, with 53% (40%-66%) of all countries having access (78% high-income versus 56% middle-income). Even in high-income countries, RNAi was not always accessible.

Conclusions: We found global disparities in access to optimal management of PH patients, disproportionately affecting low-income countries, but even existing between high-income countries. These results may provide support for initiatives to improve the outcome of PH patients worldwide in an era of new targeted therapeutic treatments.

Background: Insulin is a mainstay treatment for diabetes, but its use is associated with weight gain and hypoglycaemia. Data on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on insulin use in people with chronic kidney disease (CKD) are limited.

Methods: We conducted a post hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects of canagliflozin versus placebo on insulin use (initiation, dose intensification, reduction and discontinuation) in people with CKD and type 2 diabetes were evaluated using Cox regression models. The primary outcome was insulin initiation or a >25% insulin dose intensification (in those not receiving and receiving insulin at baseline, respectively). Effects on kidney, cardiovascular and safety outcomes by baseline insulin use were also assessed.

Results: Among 4401 participants, 2884 (65.5%) were receiving insulin at baseline; these participants were more likely to have lower estimated glomerular filtration rate, higher albuminuria and a longer duration of diabetes (all P < .001). Over a median on-treatment period of 2.0 years, canagliflozin reduced the need for insulin initiation or a >25% dose intensification by 19% compared with placebo {hazard ratio [HR] 0.81 [95% confidence interval (CI) 0.71-0.93]}, irrespective of baseline kidney function or albuminuria (both P-interaction > .10). Sustained insulin dose reductions of >50% were achieved more frequently with canagliflozin than placebo [HR 1.49 (95% CI 1.15-1.91)], although no difference in insulin discontinuation was observed between treatment arms. Effects of canagliflozin on kidney, cardiovascular and safety outcomes were consistent regardless of baseline insulin use (all P-interaction > .05).

Conclusions: In CKD and type 2 diabetes, canagliflozin reduces insulin use with consistent effects regardless of baseline kidney function. This supports the use of canagliflozin in people with CKD, not only for end-organ protection, but also to improve glycaemic control and reduce exposure to insulin and its associated adverse effects.

Background and hypothesis: A more pronounced short-term increase in single-kidney GFR (ΔskGFR) has been associated with better long-term kidney function in living kidney donors. Whether this also applies to non-donors is unknown. We evaluated whether ΔskGFR is associated with long-term risk of eGFR decline in individuals undergoing unilateral nephrectomy.

Methods: This study included 1777 participants from the SCREAM cohort who underwent radical unilateral nephrectomy in Stockholm between 2006 and 2021. The ΔskGFR was calculated as the early (1-6 months) post-nephrectomy eGFR minus 50% of the pre-nephrectomy eGFR. Multivariable Cox regression was used to study the association between Δsk-GFR and the subsequent risk of progressive eGFR decline, defined as composite of an eGFR decline >30% compared to the early (6 months) post-nephrectomy eGFR or kidney failure.

Results: Mean age at nephrectomy was 68 ± 11 years, 40% were female, 92% had kidney cancer, and median (IQR) pre-nephrectomy eGFR was 76 (61-89) ml/min/1.73 m2. Median Δsk-GFR was 11 (7-20) ml/min/1.73 m2. Pre-nephrectomy determinants of Δsk-GFR were age (inverse association) and pre-nephrectomy eGFR (positive association). During a median follow-up of 5 years (range 0.6-15 years), 178 participants developed progressive eGFR decline. Individuals with a Δsk-GFR above the median had a lower rate of progressive eGFR decline (adjusted HR: 0.58, 95% CI: 0.42-0.80), compared to those with a Δsk-GFR below the median, independent of baseline eGFR and age.

Conclusions: A stronger increase in single-kidney eGFR early after unilateral nephrectomy was associated with a lower long-term risk of progressive eGFR decline. Evaluation of Δsk-GFR could help identify patients at higher risk of progressive kidney function decline following unilateral nephrectomy.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected, with AKI often leading to CKD and vice versa. Despite research advances, their causal relationship in clinical settings remains unclear. Inflammation, oxidative stress and maladaptive repair are key factors in AKI's progression to CKD. AKI episodes may hasten CKD progression, influenced by demographics, comorbidities and treatment factors like blood pressure control. This underscores the need for careful management to prevent long-term damage. Prospective cohort studies addressing confounding factors are essential to understanding AKI's impact on CKD. These studies should use precise definitions and measurements to clarify causal pathways and risk factors. Investigating asymptomatic AKI in the general population and CKD patients could offer insights into progression mechanisms and prevention strategies. Understanding the interplay of AKI and CKD is crucial for developing interventions and improving outcomes, making it a scientific and public health priority.

Background: Several clinical trials have shown beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on kidney disease progression and cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) with and without type 2 diabetes mellitus. However, some subgroups of patients with CKD have been excluded from participation in these trials, such as patients with severely impaired kidney function, patients on dialysis and kidney transplant recipients.

Methods: The Renal Lifecycle trial (NCT05374291) is a pragmatic, international, multicentre, investigator-initiated, randomized, placebo-controlled clinical trial planned to enrol ≈1500 patients with an estimated glomerular filtration rate (eGFR) ≤25 ml/min/1.73 m2, on haemodialysis or peritoneal dialysis or after a kidney transplant and an eGFR ≤45 ml/min/1.73 m2, who will be randomized 1:1 to receive either dapagliflozin 10 mg once daily or matching placebo.

Results: The primary endpoint is a composite of heart failure hospitalization, all-cause mortality or, for those not on dialysis, kidney failure (start of dialysis >1 month, receiving a kidney transplant or death due to kidney failure). The trial is event driven, indicating that it will end after 468 first primary endpoint events have occurred, with a power of 80% and an α of 0.05 to detect a 25% relative risk reduction assuming an annual 12.5% incidence of the primary outcome. The secondary endpoints include a separate analysis of the incidence of each component of the primary endpoint in the overall trial population as well as the incidence of the combined primary endpoint in each of the three subgroups of patients. Other (exploratory) endpoints are efficacy, safety, tolerability, health-related quality of life and cognition.

Conclusion: The Renal Lifecycle trial aims to investigate the effects of the SGLT2 inhibitor dapagliflozin compared with placebo on the incidence of kidney failure, heart failure, mortality and safety in three subgroups of patients with advanced CKD.