Kidney360最新文献

Background: Long-term recurrence data on kidney stones is limited. We investigated stone recurrence in calcium-oxalate (CaOx) and calcium-phosphate (CaP) stone formers over a 10-12-year follow-up period.

Methods: We retrospectively identified patients from a surgical database with 1)CaOx or CaP stones, 2)post-surgical computed tomography imaging, and 3)at-least 10 years of clinical follow-up and imaging. Data on medical therapy (MT), defined as being on thiazide/thiazide-like diuretic, potassium citrate, and/or allopurinol, was collected. Patients' records were reviewed for stone recurrence over a 10-12-year period. Associations between stone type, medical therapy, and time to recurrence were analyzed with Kaplan-Meier survival curves and Cox proportional hazard models. Multivariate analysis was done using Cox proportional hazard model.

Results: Of the 149 individuals who met inclusion criteria, 87 (58.3%) underwent baseline 24-hour urine testing, and 46 (30.8%) were prescribed MT in the form of thiazide (26/46; 57%), potassium citrate (25/46; 54%), allopurinol (5/46; 11%). Compared to non-MT, patients on MT were more likely to have diagnosis of hypertension(p=0.008) and be hypocitraturic at baseline(p=0.01). Over a mean of 10.6 years, patients on MT had significantly fewer stone events compared to those not on MT(21.3% vs 37.5%, p=0.04) with 8(17%) individuals discontinuing their MT over the study period. Patients with predominantly CaP mineral subtype had more stone events than CaOx (64% vs 36%, p=0.006), a phenomenon likely driven by higher baseline urine pH (>6,58.8% vs 33.9%, p=0.02). By survival analysis, the impact of stone subtype and MT became apparent at follow-up month 20 and 60, respectively.

Conclusions: In a population of calcium stone formers at high recurrence risk, patients with CaOx mineral subtype and on MT had the lowest stone event rate on long-term follow-up. These findings suggest that the beneficial effect of medical therapy may take up to 5 years to become evident clinically and by surveillance imaging.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy that causes adult-onset progressive renal failure. Inflammation and the resulting fibrosis play a crucial role in the pathogenesis. In recent years, an increasing number of inflammatory markers such as MCP-1 and TNF-α, that are associated with the development and progression of ADPKD have been identified. The objective of this study was to identify and evaluate potential proinflammatory biomarkers in patients with ADPKD from the German AD(H)PKD registry.

Methods: In this exploratory pilot study, serum concentrations of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IFN-γ, MCP-1 and TNF-α were measured by multiplex immunoassay in 233 adults patients with ADPKD from the German AD(H)PKD registry and compared to an age- and sex-matched healthy control group (n = 30).

Results: IL-6, IL-8, MCP-1, TNF-α and IFN-γ concentrations were significantly higher in patients with ADPKD than in healthy controls. In addition, sex influenced the concentrations of MCP-1 and TNF-α in the ADPKD and control groups (MCP-1 male =134.8 pg/l, female=75.11pg/l; p = 0.0055; TNF-α male=26.22pg/l, female=21.08 pg/l; p = 0.0038).

Conclusion: In conclusion, patients with ADPKD have significantly higher levels of IL-6, IL-8, MCP-1, TNF-α and IFN-γ compared to healthy individuals. These findings underline that inflammation may play a crucial role in the pathogenesis of ADPKD and may be a potential target, both as biomarkers and for therapeutic interventions.

Background: Chronic kidney disease-associated pruritus (CKD-aP) has historically been associated with elevated serum phosphate (sP). Difelikefalin is a novel antipruritic agent approved for the treatment of moderate-to-severe CKD-aP in adults undergoing hemodialysis. This post hoc analysis utilized data from Phase 3 difelikefalin studies (KALM-1, KALM-2, and open-label Study 3105) to assess the role of sP in the pathogenesis of CKD-aP, and whether difelikefalin ameliorates CKD-aP in patients with and without elevated sP.

Methods: Patients with moderate-to-severe CKD-aP undergoing hemodialysis with baseline sP data were included in the analysis (KALM-1 and KALM-2, n=845; Study 3105, n=220). Assessments included correlation between 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS) score and sP.

Results: In KALM-1 and KALM-2, baseline characteristics in the overall population were similar between patients with sP ≤5.5 and >5.5 mg/dL; no significant correlation was observed between WI-NRS and sP at baseline or at Week 12. In patients receiving placebo, no correlation was observed between WI-NRS and sP at baseline or between their change from baseline to Week 12 (all p<0.05). Clinically meaningful (≥3-point) reductions from baseline to Week 12 in WI-NRS scores were reported by more patients receiving placebo with baseline sP ≤5.5 mg/dL than >5.5 mg/dL; least squares (LS) mean 37.2% versus 27.4% (odds ratio [95% CI], 0.63 [0.41, 0.97]; p=0.04). A greater proportion of patients treated with difelikefalin achieved a ≥3-point WI-NRS reduction from baseline to Week 12 versus placebo, and was similar between sP ≤5.5 and >5.5 mg/dL subgroups (LS means 51.1% vs 57.6% [p=0.20]). No significant relationships between sP and WI-NRS in patients receiving difelikefalin were identified in Study 3105 at any timepoint.

Conclusions: No correlation was observed between pruritus severity and sP, or response to placebo or difelikefalin in patients with CKD-aP undergoing HD. Difelikefalin improved itch versus placebo irrespective of baseline sP.

Background: The ratio of delta anion gap and delta bicarbonate (ΔAG/ΔHCO3) is used to detect co-existing acid-base disorders in patients with high anion gap metabolic acidosis. The ΔAG/ΔHCO3 ratio of 1.6-1.8:1 in lactic acidosis is derived from limited data using mean normal values for AG and serum HCO3. The objective of this study was to be the first to examine the ΔAG/ΔHCO3 using each patient's individual baseline AG and serum HCO3.

Methods: This was a retrospective cohort study of adult ICU patients with sepsis. Lab data from simultaneously drawn chemistry panel, including anion gap and serum lactate on admission to the ICU was obtained. Baseline AG, HCO3 and albumin measurements were obtained 1-24 months prior to ICU admission. The ΔAG/ΔHCO3 was calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3.

Results: 344 patients were included. 128 patients had normal serum lactate levels (≤1.9 mmol/L) and 216 patients had elevated serum lactate levels (>1.9 mmol/L). ΔAG/ΔHCO3 was calculated for the 216 patients who had elevated serum lactate levels (>1.9 mmol/L). The mean ΔAG/ΔHCO3 for all patients with elevated serum lactate levels was 1.20 (SD 1.50).

Conclusions: The mean ΔAG/ΔHCO3 calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3 was 1.20. The ΔAG/ΔHCO3 reported in prior literature which used mean normal AG and serum HCO3 was 1.6-1.8, highlighting that use of mean normal values affects the calculation of the ΔAG/ΔHCO3 and subsequent conclusions about underlying pathophysiology. The use of these mean normal values can result in misdiagnosis of complex acid-base disorders and inappropriate treatment. Our analysis indicates that the elevated ΔAG/ΔHCO3 is likely due to unmeasured anions contributing to an elevation in AG.

Background: In Switzerland, nephrologists must frequently obtain pre-authorizations from health insurers for certain medications/tests for individual patients. These are time consuming and outcomes are inconsistent. Clinical experience suggest inequities in access to expensive medications, related to need for and processes involved with medication pre-authorization requests.

Methods: An anonymous survey was conducted between November 2021 and March 2022 regarding experiences in applying for pre-authorizations for medications and genetic testing required for kidney care conducted among nephrologists in Switzerland.

Results: Ninety-four responses were received. The most common medications reported to require pre-approvals were rituximab, sodium glucose cotransporter-2 inhibitors (SGLT2i), mycophenolate mofetil (MMF) and eculizumab. Rebuttals were reported to be most frequently required for rituximab, eculizumab and SGLT2i, also the most frequently denied medications. Most frequent genetic testing requests were for complement and Alports spectrum disorders. Requests for genetic testing were reported to be most frequently denied for cystic renal diseases, congenital syndromes and nephrotic syndrome.Most nephrologists found requests for further information from the health insurers were seldom reasonable; 72% reported it was rarely/never possible to engage with the insurance physicians, 69% were concerned insurance physicians did not have relevant expertise. Respondents reported receiving different responses from different insurers for similar requests more frequently than from the same insurer (58% vs 8%). One in three nephrologists reported that the pre-authorizations process frequently resulted in a clinically relevant delay in treatment. Four of five respondents reported that the pre-authorization process frequently made them feel that they could not do their best for the patient.

Conclusion: From the perspective of nephrologists, the pre-authorizations process in Switzerland is cumbersome, not transparent and inequitable, may result in denial or delays of important treatment for patients and contributes to moral distress.

Background: Chronic kidney disease (CKD) poses a global health challenge, but its molecular mechanisms are poorly understood. Genetic factors play a critical role, and phenome-wide association studies (PheWAS) and genome-wide association studies (GWAS) shed light on CKD's genetic architecture, shared variants, and biological pathways.

Methods: Using data from the multicenter collaborative precision medicine cohort, we conducted a retrospective prospectively maintained cross-sectional study. Participants with comprehensive information and genotyping data were selected, and GWAS and PheWAS analyses were performed using the curated Taiwan Biobank version 2 array to identify CKD-associated genetic variants and explore their phenotypic associations.

Results: Among 58,091 volunteers, 8,420 participants were enrolled. Individuals with CKD exhibited higher prevalence of metabolic, cardiovascular, autoimmune, and nephritic disorders. Genetic analysis unveiled two closely linked SNPs, rs117026326 and rs73366469, both associated with GTF2I and CKD (r2=0.64). Further examination revealed significant associations between these SNPs and various kidney-related diseases. The CKD group showed a higher proportion of individuals with specific genotypes (CT/TT for rs117026326 and CT/CC for rs73366469), suggesting potential associations with CKD susceptibility(p<0.001). Furthermore, individuals with these genotypes developed CKD at an earlier age. Multiple logistic regression confirmed the independent association of these genetic variants with CKD. Subgroup analysis based on estimated glomerular filtration rate (eGFR) demonstrated an increased risk of CKD among carriers of the rs117026326 CT/TT genotypes (OR=1.15, 95% CI: 1.07-1.24, p<0.001; OR=1.32; 95% CI: 1.04-1.66, p=0.02, respectively) and carriers of the rs73366469 CT/CC genotypes (OR=1.13, 95% CI=1.05-1.21, p<0.001; OR=1.31, 95% CI: 1.08-1.58, p=0.0049, respectively). Additionally, men had a higher CKD risk than women at lower eGFR levels (OR=1.35, 95%: 1.13-1.61, p<0.001).

Conclusions: Our study reveals important links between genetic variants GTF2I and susceptibility to CKD, advancing our understanding of CKD development in the Taiwanese population and suggesting potential for personalized prevention and management strategies. More research is needed to validate and explore these variants in diverse populations.

Background: Contraction of interstitial fibrosis/tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive chronic kidney disease in native kidneys independent of %IFTA.

Methods: We studied kidney transplant recipients transplanted between 2000-2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density.

Results: There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 vs 0.7, p<0.0001), %IFTA (22.2% vs 7.0%, p<0.0001), and IFTA foci density (1.3 vs. 0.4 per mm2, p<0.001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (HR=1.56, p<0.0001) and higher IFTA foci density (HR=2.34, p<0.001) did. All but 4 allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure.

Conclusions: Morphometric characterization of IFTA foci density is a strong predictor of death censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.