Development of normal reference intervals for renal function in pregnancy: a secondary analysis of clinical trial data.

BACKGROUND: Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin. METHODS: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery. RESULTS: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively. CONCLUSIONS: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.

Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m² for the second and third trimesters respectively. Using the Cockcroft­Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m² for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

Surgical complications and technical failure of simultaneous pancreas-kidney transplantation: A 22-year experience from a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI:  .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.

Challenges in the development of novel methodologies for measuring glomerular filtration rate.

Measurement of glomerular filtration rate (GFR) is crucial in assessing kidney function status. Estimating GFR using clearance methodologies is cumbersome, as plasma and urinary concentrations and timed urine collections are required. Recently, a transcutaneous sensor has been developed whereby the rate of renal washout of a fluorescent marker administered intravenously allows calculation of GFR. The challenge is to ensure that the values of GFR obtained using the washout approach are in accord with those obtained conventionally.

Comparison of cystatin C-based estimated glomerular filtration rate with measured glomerular filtration rate in a pediatric cohort of patients with chronic kidney disease.

BACKGROUND: It is essential to have an accurate assessment of the renal function of patients with chronic kidney disease to monitor, treat, and predict further development of the condition. Measurement of renal function in terms of glomerular filtration rate (GFR) requires either urine or blood sampling, but especially in children, more simple methods of measurement are preferable. The main objective of this study was to examine if the estimated GFR (eGFR) calculated with different cystatin-C-based equations was comparable to the GFR measured by a radiotracer (mGFR) in pediatric patients. METHODS: In this retrospective study, 28 pediatric patients contributed with 73 pairs of measurements collected within 5 years. Bland-Altman Limits of Agreement were used to evaluate the performance and accuracy of two different cystatin-C-based estimates, the CKiDCrea-CysC and the CKiDU25 respectively, compared to an mGFR based on plasma clearance of technetium-99m-diethylenetriaminepentaacetic acid or chromium-51-ethylenediaminetetraacetic acid. RESULTS: Using the CKiDCrea-CysC equation, 58.9% of the datasets were within P10 and 87.7% were within P30. The mean difference was 4.8 mL/min/1.73m2 (standard deviation: 8.5 mL/min/1.73m2) and tended to overestimate GFR and thereby overrate the kidney function within the entire GFR range. Using the CKiDU25 equation, 53.4% were within P10 and 93.2% within P30. The mean difference was -2.9 mL/min/1.73m2 (standard deviation: 8.4 mL/min/1.73m2), but the difference varied with the GFR value. CONCLUSIONS: A cystatin-C-based eGFR provides a viable substitute for monitoring renal function in pediatric patients with chronic kidney disease. However, it has a lower accuracy than mGFR and can therefore not replace mGFR in clinical use.

Bias Found in Race-Based GFR Equations that Estimate Kidney Function.

According to this study: A systematic review and meta-analysis demonstrated bias in the race-based estimated glomerular filtration rate equations used for the diagnosis and management of kidney disease.A multifaceted approach is needed to mitigate racial disparities in chronic kidney disease outcomes.

Causal relationship between basal metabolic rate and kidney function: a bidirectional two-sample mendelian randomization study.

Background: The relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR. Methods: In this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR. Results: We found that genetically predicted BMR was negatively related to eGFR, (ß= -0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (ß= -0.040, P = 0.002), weighted median (ß= -0.04, P= 5.35×10-11) and weighted mode method (ß= -0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (ß= -0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results. Conclusion: Genetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

Trends and predictors of changes in renal function after radical nephrectomy for renal tumours.

BACKGROUND: Chronic kidney disease (CKD) is a common postoperative complication in patients who undergo radical nephrectomy for renal tumours. However, the factors influencing long-term renal function require further investigation. OBJECTIVE: This study was designed to investigate the trends in renal function changes and risk factors for renal function deterioration in renal tumour patients after radical nephrectomy. METHODS: We monitored changes in renal function before and after surgery for 3 years. The progression of renal function was determined by the progression and degradation of CKD stages. Univariate and multivariate logistic regression analyses were used to analyse the causes of renal function progression. RESULTS: We analysed the data of 329 patients with renal tumours who underwent radical nephrectomies between January 2013 and December 2018. In this study, 43.7% of patients had postoperative acute kidney injury (AKI), and 48.3% had CKD at advanced stages. Further research revealed that patients' renal function stabilized 3 months after surgery. Additionally, renal function changes during these 3 months have a substantial impact on the progression of long-term renal function changes in patients. CONCLUSION: AKI may be an indicator of short-term postoperative changes in renal function. Renal function tests should be performed in patients with AKI after radical nephrectomy to monitor the progression of functional impairment, particularly within the first 3 months after radical nephrectomy.

Multifunctional laser-induced graphene circuits and laser-printed nanomaterials toward non-invasive human kidney function monitoring.

Faced with the increasing prevalence of chronic kidney disease (CKD), portable monitoring of CKD-related biomarkers such as potassium ion (K+), creatinine (Cre), and lactic acid (Lac) levels in sweat has shown tremendous potential for early diagnosis. However, a rapidly manufacturable portable device integrating multiple CKD-related biomarker sensors for ease of sweat testing use has yet to be reported. Here, a portable electrochemical sensor integrated with multifunctional laser-induced graphene (LIG) circuits and laser-printed nanomaterials based working electrodes fabricated by fully automatic laser manufacturing is proposed for non-invasive human kidney function monitoring. The sensor comprises a two-electrode LIG circuit for K+ sensing, a three-electrode LIG circuit with a Kelvin compensating connection for Cre and Lac sensing, and a printed circuit board based portable electrochemical workstation. The working electrodes containing Cu and Cu2O nanoparticles fabricated by two-step laser printing show good sensitivity and selectivity toward Cre and Lac sensing. The sensor circuits are fabricated by generating a hydrophilic-hydrophobic interface on a patterned LIG through laser. This sensor recruited rapid laser manufacturing and integrated with multifunctional LIG circuits and laser-printed nanomaterials based working electrodes, which is a potential kidney function monitoring solution for healthy people and kidney disease patients.

Banff-based histologic chronicity index is associated with graft failure but has poor interobserver reproducibility.

BACKGROUND: Antibody-mediated rejection (AMR) often leads to chronic kidney allograft damage and is a critical cause of allograft failure. The Banff classification, used to diagnose AMR, has become complex and challenging for clinicians. A Banff-based histologic chronicity index (CI) was recently proposed as a simplified prognostic indicator. Its reliability and reproducibility have not been externally validated. METHODS: This study investigated 71 kidney allograft biopsies diagnosed with AMR. Interobserver reproducibility of the recently proposed CI and its components (cg, cv, ct, and ci) were assessed. The association between CI and allograft failure was analyzed, and CI cut-off values were evaluated by Cox proportional hazards regression and Kaplan-Meier estimator with log-rank test. RESULTS: The study confirmed the association of CI with allograft failure, but also revealed that the assessment of CI varied between pathologists, impacting its reproducibility as a prognostic tool. Only 49 (69.0%) of the biopsies showed complete agreement on the proposed cut-off value of CI < 4 or CI ≥ 4. Furthermore, this cut-off did not reliably stratify allograft failure. Notably, the cg score, which carries significant weight in the CI calculation, had the lowest agreement between observers (kappa = .281). CONCLUSIONS: While a simplified prognostic indicator for AMR is needed, this study highlights the limitations of CI, particularly its poor interobserver reproducibility. Our findings suggest that clinicians should interpret CI cautiously and consider establishing their own cut-off values. This study underscores the need to address interobserver reproducibility before CI can be widely adopted for AMR management.

Impact of delayed listing after initiating kidney transplant evaluation on transplant outcomes.

OBJECTIVE: Longer end-stage renal disease time has been associated with inferior kidney transplant outcomes. However, the contribution of transplant evaluation is uncertain. We explored the relationship between time from evaluation to listing (ELT) and transplant outcomes. METHODS: This retrospective study included 2535 adult kidney transplants from 2000 to 2015. Kaplan-Meier survival curves, log-rank tests, and Cox regression models were used to compare transplant outcomes. RESULTS: Patient survival for both deceased donor (DD) recipients (p < .001) and living donor (LD) recipients (p < .0001) was significantly higher when ELT was less than 3 months. The risks of ELT appeared to be mediated by other risks in DD recipients, as adjusted models showed no associated risk of graft loss or death in DD recipients. For LD recipients, ELT remained a risk factor for patient death after covariate adjustment. Each month of ELT was associated with an increased risk of death (HR = 1.021, p = .04) but not graft loss in LD recipients in adjusted models. CONCLUSIONS: Kidney transplant recipients with longer ELT times had higher rates of death after transplant, and ELT was independently associated with an increased risk of death for LD recipients. Investigations on the impact of pretransplant evaluation on post-transplant outcomes can inform transplant policy and practice.

Efficacy of Flexible Ureteroscopy Lithotripsy and Percutaneous Nephrolithotomy in the Treatment of Patients with Kidney Stones and Their Impact on Inflammatory Response and Renal Function.

BACKGROUND: Kidney stones are one of the most common benign diseases in urology. As technology updates and iterates, more minimally invasive and laparoscopic surgeries with higher safety performance appear. This paper explores the effectiveness of retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) in treating kidney stones, focusing on their effects on inflammatory responses and renal function. METHODS: We conducted a retrospective analysis of 200 patients with kidney stones treated in our hospital between June 2019 and June 2023. 100 patients who underwent RIRS were included in the RIRS group. Another 100 patients who underwent PCNL treatment were included in the PCNL group. The intraoperative blood loss, operation duration, and hospitalization time of the two groups of patients were recorded and compared. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors in the serum of the two groups of patients: [serum amyloid A (SAA), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRP)] and renal function index [blood urea nitrogen (BUN), creatinine (Scr) and serum cystatin (Cys-c)]. The two groups of patients were recorded separately: Postoperative complications and stone-free rate. RESULTS: Operation duration was longer for the RIRS group than the PCNL group, which exhibited significantly less intraoperative blood loss and shorter hospital stays (p < 0.05). Before surgery, there was no statistically significant difference in the serum levels of SAA, IL-6, and CRP between the two groups of patients (p > 0.05). On the first day after surgery, the serum SAA levels in both groups were lower than before surgery, IL-6 and CRP levels were higher than before surgery, and the serum levels of SAA, IL-6, and CRP in the RIRS group were significantly lower than those in the PCNL group. The difference was statistically significant (p < 0.05). Before surgery, there was no statistically significant difference in the serum BUN, Scr, and Cys-c levels between the two groups of patients (p > 0.05). On the first day after surgery, the serum BUN, Scr, and Cys-c levels of the two groups of patients were significantly higher than those before surgery. The serum BUN, Scr, and Cys-c levels of the RIRS group were significantly lower than those of the PCNL group, and the difference was statistically significant (p < 0.05). Both surgical methods have sound stone-clearing effects regarding long-term stone clearance rates 1 month and 3 months after surgery (p > 0.05). PCNL had a better stone clearance rate on the 2nd postoperative day (p < 0.05). The incidence of postoperative complications in the RIRS group was significantly lower than that in the PCNL group, and the difference was statistically significant (p < 0.05). CONCLUSION: For kidney stones ≤2 cm, PCNL showed higher stone clearance rates on the second postoperative day. However, RIRS and PCNL demonstrated adequate long-term stone clearance at 1 and 3 months post-surgery. Both surgical methods are safe and effective, and RIRS is safer than PCNL. Compared with PCNL, RIRS is a new method of kidney stone operation, which has less trauma to the patient's body and fewer complications after the operation, speeding up the recovery process of the patient.

Application of the European Kidney Function Consortium Equation to Estimate Glomerular Filtration Rate: A Comparison Study of the CKiD and CKD-EPI Equations Using the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021).

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Measurement of Glomerular Filtration Rate in Patients Undergoing Renal Surgery for Cancer: Estimated Glomerular Filtration Rate versus Measured Glomerular Filtration Rate in the Era of Precision Medicine.

BACKGROUND: In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. SUMMARY: This paper delves into the significance of accurately measured glomerular filtration rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional glomerular filtration rate (GFR) estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. KEY MESSAGE: Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

Evaluation of differential renal function in children - a comparative study between magnetic resonance urography and dynamic renal scintigraphy.

BACKGROUND: Urinary system anomalies, both congenital and acquired, constitute a relatively common clinical problem in children. The main role of diagnostic imaging is to determine early diagnosis and support therapeutic decisions to prevent the development of chronic renal disease. The aim of this study was to evaluate the utility of magnetic resonance urography (MRU) in assessment of urinary system in children, by comparing differential renal function calculated using MRU with dynamic renal scintigraphy (DRS). MATERIALS AND METHODS: The study group consisted of 46 patients aged 1 week to 17 years (median 7 (0.5; 13) years, 17 (37%) girls, 29 (63%) boys), who underwent dynamic renal scintigraphy due to various clinical reasons. All participants underwent MRU, which was used to measure differential renal function. Functional analysis was performed using dedicated external software (CHOP-fMRU and pMRI without prior knowledge of DRS results. MRU results acquired using pMRI were assessed for inter and intraobserver agreement. RESULTS: Statistical analysis of the results showed excellent agreement between MRU and DRS in measuring differential renal function with Pearson correlation coefficient 0.987 for CHOP-fMRU and 0.971 for pMRI, p < 0.001. Interclass correlation coefficient (ICC) for these programs was 0.987 (95% CI 0.976-0.993) and 0.969 (95% CI 0.945-0.983) respectively, p < 0.001. The Bland-Altman 95% limits of agreement for CHOP-fMRU results vs. DRS was - 6.29-5.50 p.p. and for pMRI results vs. DRS - 9.15-9.63 p.p. The differential renal function measurements calculated in pMRI showed excellent intraobserver and interobserver agreement with ICC 0.996 (95% CI 0.994-0.998) and 0.992 (95% CI 0.986-0.996) respectively, p < 0.001. CONCLUSIONS: The study showed no significant differences between magnetic resonance urography and dynamic renal scintigraphy in calculating differential renal function. It indicates high utility of MRU in the evaluation of urinary system in children.

Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.