Reduction In GFR Research Articles

Clinical experience of using the ckd progression rate calculator to stratify a group of elderly patients with type 2 diabetes with a very high risk of cardiovascular outcomes

Objective: to analyze the clinical experience of using the CKD progression rate calculator to stratify the prognosis of elderly patients with DM2, belonging to a very high cardiovascular risk group. Material and methods: to determine the systemic coronary risk of elderly patients with DM2, the generally accepted and most relevant SCORE2 and SCORE2-OP algorithms were used to assess the 10-year risk of fatal and nonfatal cardiovascular events. Further more accurate stratification of the risks of CKD was performed using a prognostic Calculator of the rate of progression of CKD in elderly patients with DM2, developed at the Department of Endocrinology of the Samara state medical university. Results: as a clinical example, two 69 and 70-year-old patients were randomly selected from the group of participants used in the development of the mathematical model of the Calculator. According to the SCORE2 and SCORE2-OP algorithms, both patients were assigned to a very high-risk group of cardiovascular diseases, the values of which were 33% for patient XXX; 24% for patient YYY, excluding concomitant DM2 and CKD. To clarify the clinical prognosis, an original Calculator was used, which demonstrated different characteristics of the CKD progression rate in these patients (“low” and “high” with a cut-off value of the GFR reduction index of 3.83 ml/min/1.73 m2 per year), despite the identity of the parameters of the clinical and laboratory status. Conclusions: the use of traditional ASSR risk assessment scales for predicting outcomes in a cohort of elderly with DM2 has significant limitations, since most patients of older age groups fall into a homogeneous group of very high risk without the possibility of further stratification; the use of a Calculator for the rate of progression of CKD allows you to refine the prognosis, optimize the program of follow-up and determine indications for prescribing drugs with proven nephroprotective the effect in elderly patients with DM2.

The use of a clinical calculator to determine the rate of development of chronic kidney disease in elderly patients with type 2 diabetes mellitus

Aim – to develop an applied prognostic calculator for the rate of progression of CKD in elderly patients with type 2 diabetes, which makes it possible to identify a group of high rate of GFR reduction in conditions of routine outpatient admission. Material and methods. 69 clinical indicators were studied, the interrelationships and significance of differences in parameters in the groups identified according to the original diagnostic parameter, the glomerular filtration rate reduction index with a threshold value of 3.83 ml/min/1.73 m2 per year, above which the rate of progression of CKD was considered high. Results. By using regression analysis, significant factors for the prognostic calculator were identified: the duration of diabetes and insulin therapy, concomitant diagnosis of obesity, pulse in the ankle artery, severe stage of polyneuropathy, risk group IV of hypertension, treatment with sulfonylureas, the number of antihypertensive drugs taken. When evaluating the information capacity and predictive ability of the calculator, the area under the AUC ROC curve was 0.89 (0.80; 0.99) p 0.001, which characterizes the quality of the diagnostic technique as high. Conclusion. The presented calculator gives the doctor the opportunity to identify a group of patients with the risk of rapid progression of CKD directly on an outpatient basis.

P193 BLOOD PRESSURE CHANGES IN THE IMMEDIATE POST OPERATIVE PERIOD OF LIVE-RELATED KIDNEY DONORS IN AN INDIAN COHORT: SHOULD WE BE LOOKING MORE?

Background & Objective: Kidney donation is associated with physiological changes (hyperfiltration, changes in renin-angiotensin-aldosterone system & vascular tone) and its effects can be more pronounced in the elderly. The immediate reduction in GFR after nephrectomy can pose a risk for development or worsening of hypertension. There is a paucity of data determining the impact of reduced GFR on BP in post-operative period. Our study aims to analyze the hemodynamics in the post-operative period after nephrectomy. Methods This was a prospective observational study of 30 donors who underwent live-related Donor Nephrectomy. Parameters like demography, pre- and post-nephrectomy BP (reading taken daily for every 3 hours till post-operative day (POD) 4 using BPL oscillometric device) were studied. Continuous variables were were expressed as mean & standard deviation. The Student's paired t-test was used for comparison using SPSS Windows software. Results The age of donors ranged from 23-73 years. Mean SBP/DBP was 112.69 ± 5.44/76.77 ± 3.78 mmHg in donors <50 years, while in donors aged >50 years the mean SBP/DBP was 126.6 ± 7.9/81.7 ± 3.82 mmHg. Post-donation in donors aged <50 years (17 donors), mean S.B.P/DBP on POD 1 was 108.38 ± 4.77/76.20 mmHg followed by 108.92 ± 4.24/76.84,110.12 ± 5.42, 114 ± 4.8/78.88 ± 2.66 on POD-2, 3 & 4 respectively. After Nephrectomy in donors aged more than 50 years(13 donors), mean SBP/DBP on POD 1 was 124.38 ± 4.56/78.20 mmHg followed by 126.40 ± 4.54/79.88,127.72 ± 6.22, 130.22 ± 3.8/84.58 ± 4.24 on POD-2, 3 & 4 respectively. The BP on POD-4 was significantly higher in donors with age more than 50 years than donors with age less than 50 years (p<0.05). Conclusion: After nephrectomy, blood pressure changes in the immediate post-operative period in the elderly need to be monitored closely. Frequent BP monitoring after nephrectomy should be implemented to determine risk of HTN in kidney donors.

#530 Cardiorenal effects of dual blockade with ACE inhibitors and ARBs among people with CKD: emulation of a reference trial (ONTARGET) using CPRD

Abstract Background and Aims Cardiovascular disease (CVD) is a leading cause of death globally, and individuals with chronic kidney disease (CKD) are at increased risk. Results from the ONTARGET trial, in conjunction with the ALTITUDE and VA-Nephron-D studies, led to an end of recommendations for dual ACE inhibitor and ARB therapy due to an increase in acute kidney injury. However, these studies had low power to address long-term kidney outcomes and there remains uncertainty about whether dual therapy could be effective at reducing adverse cardiovascular and renal outcomes in patients with CKD. Observational data provides an opportunity to explore such hypotheses in subgroups underrepresented in trials and with power and follow-up enabling estimation of risk of rare outcomes. We aimed to use ONTARGET to perform a reference trial emulation analysis, before extending analysis to explore treatment effectiveness of dual ARB and ACEi use vs ACEi alone in preventing cardiovascular and renal outcomes among those with CKD. Method Using routinely-collected data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked with Hospital Episode Statistics secondary care data, we applied the ONTARGET trial eligibility criteria to patients prescribed an ARB/ACE inhibitor between 1/1/2001-31/7/2019. As the number of patients receiving prescriptions for both medications on the same day was likely to be small in routine care, we used an operational definition to capture dual users. Outcomes included ONTARGET primary cardiovascular composite outcome of cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure and a composite renal outcome of ≥50% reduction in GFR or end-stage kidney disease (ESKD). Within the trial-eligible cohort, outcomes of interest were compared between groups prescribed dual therapy vs ACE inhibitors alone using a propensity-score—weighted time-to-event analysis using a Cox proportional hazards model. Conditional on successfully benchmarking results against the ONTARGET trial, we explored treatment effect heterogeneity by chronic kidney disease (CKD) at baseline, with CKD defined as estimated glomerular rate (eGFR) < 60 ml/min/1.73 m2. Results 412,406 trial-eligible patients in CPRD were included in analysis. Among those with non-missing eGFR at baseline, 37% had CKD (Table 1). We found similar effectiveness of dual therapy and ACE inhibitors in reducing the risk of the primary composite cardiovascular outcome (HR 0.98 (95% CI: 0.93, 1.03), consistent with the ONTARGET trial results (HR 0.99 (95% CI: 0.92, 1.07), with no evidence of heterogeneity by CKD (P-value for interaction = 0.14). However, dual therapy use was associated with a greater risk for the composite renal outcome compared to ACE inhibitor, HR 1.24 (95% CI: 1.14, 1.35), with no evidence of heterogeneity by CKD (P = 0.93) (Fig. 1). Analysing components of the composite renal outcome separately gave consistent results (≥50% reduction in GFR: HR 1.22 (95% CI: 1.12, 1.33); ESKD: HR 1.34 (95% CI: 1.24, 1.57)), as did a post-hoc sensitivity analysis by proteinuria status (no proteinuria: HR 1.28 (95% CI: 1.03, 1.59); proteinuria: 1.27 (95% CI: 1.08, 1.49)). Conclusion We found evidence that dual therapy use was associated with increased risk of renal outcomes in both those with and without CKD at baseline. Applying a reference trial emulation approach and successfully benchmarking findings against ONTARGET, where confounding was not present due to randomisation, provides confidence in the validity of these results.

Excess body weight, duration of insulin and antihypertensive therapy slow down the rate of progression of chronic kidney disease in type 2 diabetes

Objective: to study and clinically substantiate the relationship between overweight and the dynamics of CKD progression in patients with type 2 diabetes of different age groups using the diagnostic parameter Index of glomerular filtration rate reduction. Material and methods: a single-stage cross-sectional observational study of clinical indicators in a population sample of patients with type 2 diabetes of different age groups was performed, patterns of relationships, significance of differences in mean values and measures of influence (OR (95%CI)) were studied between the indicators of BMI, the stage of obesity and the presence of a diagnosis of obesity in the anamnesis and the original calculated diagnostic parameter, the Index of glomerular filtration rate reduction (RI_GFR), which allows to give an objective quantitative characteristic of the rate of progression of CKD. Results: significant correlations were established between RI_GFR and indicators of age, BMI, DM experience and duration of insulin therapy, a significant inverse relationship with BMI was noted only in the older group; when analyzing differences in the average values of clinical indicators in the groups of rapid and slow progression of CKD, divided by the threshold value of RI_GFR, significant factors affecting the rate of progression were determined CKD: DM experience, duration of insulin therapy, BMI; the logistic regression analysis determined the measure of the influence of the above factors on the dynamics of GFR reduction, confirmed its significance; when analyzing the factors of drug treatment in the elderly group, it was revealed that an integrated approach to the appointment of antihypertensive therapy (prescribing drugs of three or more groups) significantly reduces the risk of rapid progression of CKD. Conclusions: the most significant risk factors for the high rate of progression of CKD in patients with type 2 diabetes and overweight in the general sample and in patients of the older age group are the length of diabetes and duration of insulin therapy; the dynamics of GFR reduction in patients with type 2 diabetes of different age groups is interrelated with BMI, and in patients with overweight CKD progresses more slowly; an integrated approach to prescribing antihypertensive therapy (prescribing drugs of three or more groups) in elderly patients with type 2 diabetes significantly reduces the risk of rapid progression of CKD.

The effect of knee replacement on renal function in patients with hypertension and type 2 diabetes mellitus

Objective: to evaluate the effect of knee replacement on kidney function in patients with hypertension and type 2 diabetes mellitus. Materials and methods: at stage 1, 308 people suffering from hypertension (GB), stage III osteoarthritis of the knee joint (OA CS), type 2 diabetes mellitus (DM) were examined. GB occurred in 308 people, DM — in 66 people, and OA CS — in 216 people. Depending on the presence of OA CS, observation and comparison groups were identified. Within each group, subgroups are distinguished by the presence of SD: subgroup 1 (n=170) — OA CS +GB, subgroup 2 (n=46) — OA CS+GB+SD, subgroup 3 (n=72) — GB, subgroup 4 (n=20) — GB+SD. At stage 2, the dynamics of GFR after total knee arthroplasty (TEP CS) in subgroups 1 and 2 and against the background of AGT therapy in subgroups 3 and 4 were evaluated. Results: at the 1st stage, it was found that the proportion of people with GFR 60 ml/min/1.73 m2 was significantly higher in subgroup 1 (OA CS+GB) compared with subgroup 3 of patients with GB without joint pathology (40.6% vs. 12.5%, p0.01). The presence of DM in patients with GB significantly affected renal filtration function, which is reflected in an increase in serum creatinine levels in subgroup 4 (GB+DM) by 20.02% and a decrease in GFR by 15.35%.Against the background of the performed TEP in the group with GB, 64.06% had a stable GFR value or its increase, and in the subgroup of GB+ DM after TEP, 72.41% of patients had an increase or stable state of renal filtration capacity. At the same time, during the same follow-up period in the comparison group (in patients with GB without comorbid conditions), only 39.13% of cases had stable GFR values, and a decrease in GFR was recorded in 60.87%. At the same time, the dynamics of GFR values manifested itself in an increase of 11.19% in patients of subgroup 5 (TEP CS + GB) and by 12.47% in the group of the described knee joint intervention with a combination of GB and DM. In patients with controlled hypertension, GFR decreased by 6.6%. Conclusion: knee replacement in patients with hypertension and type 2 diabetes mellitus can slow down the rate of GFR reduction.

Effect of Intravitreal Anti-Endothelial Growth Factor Agents on Renal Function in Patients With Diabetes Mellitus

BackgroundIntravitreal administration of vascular endothelial growth factor inhibitors (anti-VEGF) is the treatment of choice in retinal pathology associated with type 2 diabetes mellitus (DM2). We aimed to analyze the effect on renal function in patients with DM2 after intravitreal anti-VEGF administration. MethodsSingle-center retrospective and observational study of patients with DM2 with and without chronic kidney disease (CKD). We analyzed the evolution of renal function after anti-VEGF onset, compared with a control group. ResultsWe included 45 patients (55.6% male) who received anti-VEGF therapy. Mean age was 74.4±11.5 (50-91) years. These were compared with 45 patients with similar characteristics. After 12-months, 76.3% had CKD with a mean reduction in estimate glomerular filtration rate (eGFR) of 19.4%. Nine patients (20%) had a >25% reduction in eGFR, and three patients (6.7%) had a >50% reduction in GFR. At 24-months, 80% of patients had CKD with a mean eGFR drop of 28%. The mean eGRF slope of patients who had received anti-VEGF treatment was 10 ml/min/year compared to 1,5 ml/min/year in the control group (p<0.05). After the first administration, five patients (17.2%) in the CKD group required renal replacement therapy during follow-up (mean time 22±12 months). Main risk factors for need of dialysis were age, presence of previous CKD, and baseline proteinuria. ConclusionIntravitreal anti-VEGF administration is a risk factor for CKD and rapid progression to end-stage kidney disease in patients with previous CKD. Knowing these drugs' implications is crucial to avoid CKD progression and opportunely limit their use in certain patients.

Study on serum uric acid concentration and serum uric acid/creatinine ratio in patients with type 2 diabetes

Objectives: 1. Determination of serum uric acid concentration and serum uric acid/creatinine ratio in patients with type 2 diabetes. 2. Find out correlations between serum uric acid, serum uric acid/creatinine ratio and some clinical and paraclinical characteristics in patients with type 2 diabetes. Materials and methods: 141 patients with type 2 diabetes, at the Examination Department of Khanh Hoa Provincial General Hospital from April 2022 to June 2023; method: cross-sectional descriptive study, data processing using SPSS 18.0 software. Results: men account for 56%, women account for 44%. The average age was 55.3 ± 9.7 year. The average time to detect diabetes is 9.4 ± 6.6 year. The rate of hypertension is 42.6%. The obesity rate is 26.2%. Average waist circumference: 81.06 ± 8.9 cm. Good fasting blood glucose control accounts for 39.0%, good HbA1c control accounts for 36.9%. The average GFR is: 83.42 ± 22.81 (ml/min/1.73m2), GFR reduction accounts for 11.3%, CKD accounts for 43.9%. The average serum UA concentration was: 345.87 ± 98.57 mmol/l, the average serum UA/Cre value was: 4.23 ± 1.3, with 23.4% increased serum UA. There is a negative correlation between UA and GFR, r = - 0.409. UA concentration in the group with CKD was higher than the group without CKD, p &lt; 0.05. There is an association between UA according to CKD stage, p &lt; 0.001. There is a relationship between UA/Cre according to CKD stage, p &lt; 0.0001. There is a statistically significant relationship (p &lt; 0.001) between UA concentration and urinary ACR level. Multivariable linear regression equation: GFR = 118.122 + 5.449*UA/Cre – 0.674*Age - 3.563*Urea - 0.014*ACR, with R2 = 64.1%, B = 5.449, p &lt; 0.001. ROC curve analysis: Serum UA value: AUC = 0.767, p &lt; 0.001, PI: 433.5, Se: 56.3%, Sp: 87.2%). Serum UA/Cre value: AUC = 0.131, p &lt; 0.05. Conclusions: Serum UA/Cre ratio has prognostic value for CKD in patients with type 2 diabetes (R2 = 64.1%, B = 5.449). Serum UA concentration is valuable in predicting the occurrence of CKD in patients with type 2 diabetes (AUC = 0.767, cut-off point is 434 (µmol/l), with Se: 56.3% and Sp: 87.2%. Key words: diabetes, serum uric acid, serum uric acid/ creatinine ratio.

Rhabdomyolysis aggravates renal iron accumulation and acute kidney injury in a humanized mouse model of sickle cell disease

Individuals with sickle cell disease (SCD) are at greater risk of rhabdomyolysis, a potentially life-threatening condition resulting from the breakdown of skeletal muscle fibers. Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis. Chronic kidney and cardiovascular disease, which account for SCD mortality, are long-term consequences of AKI. Although SCD elevates the risks of rhabdomyolysis-induced sudden death, the mechanisms that underlie rhabdomyolysis-induced AKI in SCD are unclear. In the present study, we show that, unlike their control non-sickling (AA) counterparts, transgenic homozygous SCD (SS; Townes model) mice exhibited 100% mortality 8–24 h after intramuscular glycerol injection. Five hours after glycerol injection, SS mice showed a more significant increase in myoglobinuria and plasma creatine kinase levels than AA mice. Basal plasma heme and kidney tissue iron levels were significantly higher in SS than in AA mice. In contrast to AA, glycerol-induced rhabdomyolysis aggravated these parameters in SS mice. Rhabdomyolysis also amplified oxidative stress in SS compared to AA mice. Glycerol-treated SS mice exhibited worse renal function, exemplified by a reduction in GFR with a corresponding increase in plasma and urinary biomarkers of early AKI and renal tubular damage. The free radical scavenger and Fenton chemistry inhibitor, TEMPOL, ameliorated rhabdomyolysis-induced AKI in the SS mice. These findings demonstrate that oxidative stress driven by renal iron accumulation amplifies rhabdomyolysis-induced AKI in SCD mice.

#5705 EFFICACY AND SAFETY OF SACUBITRIL/VALSARTAN IN PATIENTS WITH STAGE 3B-5 CKD AND HYPERTENSION

Abstract Background and Aims Sacubitril/valsartan (SV) plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure. However its effects on kidney function in people with moderate to severe chronic kidney disease (CKD3b-5) are unknown. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with stage 3b-5 CKD and hypertension. Method In this randomized, double-blind, 3-month trial, patients with stage 3b-5 CKD and hypertension were randomly assigned to sacubitril/valsartan treatment group (n = 44, the doses of SV were up-titrated to sacubitril/valsartan 400 mg), and conventional antihyperensive treatment group (n = 40). The primary outcome was reduction in GFR from baseline at week 12. Results In total, 44 participants were assigned to sacubitril/valsartan group and 40 to crontol group (conventional antihyperensive group). Baseline measured GFR was 29.94±11.83, 27.86±10.14 mL/min/1.73 m2, respectively. There was no difference in measured GFR (P = 0.064). At week 12, there was a reduction in measured GFR in control group: 27.86±9.15 versus 22.03±11.41, but there was no significant difference (P = 0.155). Sacubitril/ valsartan could improve eGFR: 29.94±11.83 versus 32.05±14.57 (P = 0.018). We also observed that, compared with control group, sacubitril/valsartan decreased albuminuria: reductions in urinary albumin:creatinine ratio (ACR) in sacubitril/valsartan group was 89.5mg/g and reductions in urinary ACR in control group was -44.55mg/g. At week 12, Sacubitril/valsartan provided a significantly greater reduction in office mean sitting (ms) systolic BP (msSBP) than control group (20.75mmHg vs 12.88mmHg, P = 0.046). There was no serious adverse events in both groups. The incidence of hyperkalemia (potassium≥5.5 mmol/L) was 4.5% in SV group and 7.5% in control group. Conclusion The present data suggested that, in patients with stage 3b-5 CKD and hypertension, Sacubitril-valsartan could improve kidney function and decrease albuminuria, and was generally safe and well tolerated.

#5554 ROLE OF THE TUBULAR EPITHELIAL CELL NLRP3 INFLAMMASOME DURING HYPERGLYCEMIA AND GLUCOSURIA IN DIABETES

Abstract Background and Aims Diabetes is a prominent risk factor for the progression of CKD because hyperglycemia and glucose filtration increase the hemodynamic and metabolic workload to the nephrons, which imposes adaptive mechanisms. Tubules adapt to diabetes by enlargement and epithelial cell hypertrophy but an exceeding metabolic workload promotes oxidative stress, cytokine signaling and tubular epithelial (TEC) cell demise leading to tubular atrophy and interstitial fibrosis. Several studies propose a role of the NLRP3 inflammasome in tubulointerstitial inflammation in diabetic and non-diabetic kidney disease. The NLRP3 inflammasome is a sensor of cellular damage responsible for regulate the IL-1β and IL-18 production, playing important role during the progression of CKD. However, the role of NLRP3 in diabetes-induced tubular adaptation is unknown. Method scRNAseq analysis showed previously that the TECs do not express NLRP3 or inflammasome components. However, a group of patients diagnosed with Cryopyrin-Associated Autoinflammatory Syndromes, have a mutation that overexpress NLRP3, which is associated with chronic and systemic inflammation. To investigate the role of NLRP3 on tubular cells under diabetes conditions, we generated a mouse line by crossing mice bearing LoxP-target A350V allele with Pax8-driven Cre transgenic mice. Animals carrying the A350V allele have overexpression of NLRP3 in tubular cells. The combination of unilateral nephrectomy and treatment with multiple low doses of streptozotocin (60 mg/Kg) accelerate the kidney injury caused by hyperglycaemia. Kidney function, histology and gene expression were evaluated at the end of 16 weeks of diabetes. In vitro experiments carried out using TECs isolated from Pax8-A350V, and stimulated with LPS (1µg/ml) and/or ATP (20 mM). Results In silico analysis showed TECs do not express NLRP3 or inflammasome components. A350V-TECs under inflammasome activation did not produce IL-1β or IL-18. However, the Nlrp3 overexpression upregulated kidney injury markers, as well IL-6 and TNF. Moreover, the increase in kidney inflammation was associated with significative upregulation of fibrosis markers (Tgfb1, Asma, and Fn1) and extracellular molecules (Ctgf, AnxaII, and Chd2). Diabetic mice carrying the A350V mutation did not have significative differences in blood glucose, albuminuria, or body weight when compared with diabetic control mice. The overexpression of NLRP3 in tubular cells was associated with significative reduction in GFR and BUN when compared with controls mice, even though no differences in tubular injury markers observed. Furthermore, Pax8-A350V diabetic mice expressed significantly more Nlrp3 and Il1b than control group. Although, no differences observed in cryopyrin staining. Conclusion Our data suggest the NLRP3-associated damage in tubular epithelial cells occurs in a non-canonical manner.

#5026 ESTIMATED PROXIMAL TUBULE FLUID PHOSPHATE CONCENTRATION AS AN ELEMENT OF DECREASED RENAL FUNCTION IN PATIENTS UNDERGOING UNILATERAL NEPHRECTOMY

Abstract Background and Aims Patients with chronic renal failure (CRF) develop early alterations in mineral metabolism called Chronic Kidney Diseases Mineral Bone Disorders (CKD-MBD), detectable with the available markers (PTH, Ca, Ps) only in the most advanced stages of disease. Recent evidence suggests that the early development of CKD-MBD is related to the nutritional phosphorus intake and the reduction of the number of nephrons (renal functional reserve). Infact with the reduction in the nephrons number, compensation systems must be activated for the maintenance of the phosphoric balance with an increase in urinary phosphate and in the concentration of phosphorus in the single nephron (ePTFp). Therefore, the measurement of ePTFp has been proposed as a new early marker of CKD-MBD and effective renal functional reserve. Threshold values of ePTFp (2.2 mg/dl) have been identified to indicate patients with reduced renal functional reserve and therefore at increased risk of progression of renal damage. The measurement of residual renal function with ePTFp may be a useful parameter to be evaluated in patients who undergo unilateral nephrectomy due to renal neoplasia. In fact, post-nephrectomy some patients have a high reduction of the renal function not identified by preoperative GFR assessment or other risk factors. In these patients, ePTFp could represent a measure of pre nephrectomy kidney functional reserve and thus indicate the risk of reduce renal function after nephrectomy. The aim of the study was to evaluate the relationship between pre-operative ePTFp and renal function after nephrectomy. Methods This is a transversal monocentric observational study. From January 2022 to November 2022, we enrolled patients diagnosed with renal cell carcinoma for which has been indicated unilateral nephrectomy surgery. In all patients we evaluated pre nephrectomy and three months after surgery, renal function, and ePTFP with the formula [ePTFp = (Phosphaturia / creati-ninuria) x creatininemia x 3,33]. 30 subjects with normal renal function (eGFR 100±10 ml/min, no proteinuria) were evaluated for the ePTFp reference values. Results We evaluated 13 patients: age 57.5 ± 13.6; Cr 1.48±0.7 mg/dl; eGFR 58.5 ± 23.3, mil/min; Pi, mg/dl 3.2± 0.6; Ca 9.9± 0.6 mg/dl,PTH 58,8± 41 pg/ml FA 176,7± 108 IU/L, proteinuria 500±150 mg 24H. Compared to the control population (GFR 100 ml/min) the 24-hour phosphaturia was no different while ePTFp was increased 2.1± 0.9 vs 1.2±0.2 mg/dl; p: 0.05. In the post-nephrectomy assessment, creatinine and GFR were stable (Cr 1.48±0.7 vs 1.5 ±0.7 mg/dl; p: n.s; eGFR 58.5 ± 23.3, vs 56.5 ± 22.3, mil/min; p: n.s), while ePTFp was increased (ePTFp pre 2.1± 0.9 vs ePTFp post 3.3± 2.7; p&amp;lt;0.01). Patients with pre-nephrectomy ePTFP ≥ 2.2 mg/dl (n. 6, eGFR 56.5 ± 20.3, proteinuria 550±100 mg/24h) had a greater renal function reduction post nephrectomy (mean GFR delta -9.5±2 ml/min) respect to patients with pre-nephrectomy ePTFP &amp;lt;2.2 mg/dl (n. 7, eGFR 59.7 ± 24.3, proteinuria 500±200 mg/24h; mean GFR delta -0.5±2 ml/min; p: 0.05). In all the population there was direct correlation between ePTFp and the reduction of GFR post nephrectomy (r: 0.667; p: 0.05). Conclusion In our patients ePTFp was higher than the control group and correlate with the entity of the GFR reduction post nephrectomy. The group with a preoperatory ePTFp ≥ 2,2 mg/dl had a higher post nephrectomy GFR reduction. These results suggest that ePTFp identify the pre nephrectomy kidney functional reserve. In particular and ePTFp higher than limits highlighted in the literature (2.2 mg/dl) pre nephrectomy identify a greater risk of kidney function reduction post nephrectomy. ePTFp may be proposed as a parameter to identify patients with higher risk of decreased renal function post nephrectomy.

#6910 PREDICTORS OF KIDNEY FUNCTION DECLINE IN LIVING KIDNEY TRANSPLANTATION DONORS

Abstract Background and Aims After nephrectomy kidney transplant donors lose 50% of their renal mass. Shortage of donors and long waiting list for deceased donor transplantation expanded the living donor criteria. The aim of this study to identify pretransplant donor related factors associated with renal function decline. Method We retrospectively studied LDKT donors from one transplant center in the period 2013 -2022. Data was retrieved from medical history charts and national electronic database system. Demographic characteristics as age, gender and relation to the recipient, patients preference to donate the kidney with higher measured split GFR, the presence of diabetes, hypertension, hyperlipidemia and BMI &amp;gt;30kg/m2 were analysed. Estimated GFR by CKD EPI was notified prior donation, one and two years afterwards. In a multivariate regression analysis the reduction ratio of CKD EPI was explored as dependent variable. Results We studied 121 donors. The average age at time of transplant was 59.18 ± 10.99 years. Donors’ average eGFR was 91.53 ± 18.62 mL/min. Donor's age and eGFR were significantly correlated (p &amp;lt; 0.0001, r=r−0.529). Male donors were 37 (30%), 11 (9%) were unrelated to recipients, 9(7%) had BMI&amp;gt;30, 17 (14%) diabetes, 53 (44%) hypertension 5 (4% hyperlipidemia), and 65 (52%) had more then one comorbidity combined. Eight of donors (7%) decided to donate the better kidney. CKD EPI declined to 68.17±18.62 ml/min at first and 66.01±21.29 ml/min at the second year. The RR of 24.53 ± 20.60 % and 27.62±18.76% raised on yearly bases, respectively. In the univariate analysis of the GFR declination at the first year BMI&amp;gt;30 kg/m2 was associated with higher reduction of GFR (β=0.318, P = .003). At the second year the presence of diabetes emerged as worsening factor of GFR (β=0.227, P = .034) and BMI&amp;gt;30 kg/m2 kept its significance (β=0.426, P = .000). All the other parameters showed no significant associations to the GFR decline. In the multivariate analysis BMI&amp;gt;30 kg/m2 remained as most powerful predictor at 12 months reduction of eGFR. Conclusion Patients with diabetes and especially with obesity are at higher risk of rapid decline in kidney function after kidney donation. Careful assessment prior kidney donation should weight the risks.

Clinical calculator for the prognosis of rapid progression of chronic kidney disease in patients with type 2 diabetes mellitus

Aim. To develop an applied clinical calculator for the prognosis of rapid progression of CKD in patients with type 2 diabetes, which allows to identify a group of patients at risk of a high rate of decrease in GFR of diabetes in outpatient admission, to assess its informativeness, resolution and diagnostic significance.Material and methods. A single-stage cross-observational study of clinical status indicators was performed in a population sample of patients with type 2 diabetes. Primary medical data were collected using the AWPE 2.0 program; 150 protocols of outpatient consultations, including 69 clinical indicators, were selected according to the compliance criteria. Based on the results of a comprehensive analysis of the relationship between the indicators of clinical status and the stages of development of CKD in type 2 diabetes, the most significant factors of progression of diabetic kidney damage are identified; the original diagnostic parameter "GFR reduction Index" is proposed and clinically justified, which allows to give an objective quantitative characteristic of the dynamics of the pathological process; the measure of the influence of diagnostically significant predictors on the rate of GFR reduction is determined by regression analysis; a logistic model is constructed, on the basis of which a prognostic calculator for rapid progression of CKD is developed.Results. Quantitative assessment of the contribution of individual clinical indicators to the rate of progression of CKD allowed us to identify the following significant factors: duration of diabetes and insulin therapy, acute myocardial infarction in history, age, BMI, concomitant retinopathy, pulsation on the popliteal artery, risk group IV hypertension, treatment with sulfonylureas (without differentiated assessment by pharmacological groups), calcium antagonists; when evaluating the informativeness and predictive ability of the calculator, the area under the AUC ROC curve was 0,90 (0,82; 0,98), p&lt;0,001, which characterizes the quality of the diagnostic technique as very high.Conclusion. The original diagnostic parameter "Glomerular filtration Rate reduction Index" allows us to get a more detailed and accurate idea of the patterns of progression of CKD in DM, the applied clinical calculator of rapid progression of CKD allows us to identify a group of patients at risk of a high rate of GFR reduction, with a high level of diagnostic significance in outpatient settings.

SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes' mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.

SGLT-2 Inhibitors and Renal Outcomes in Non-Diabetic Patients: A Systematic Review

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown positive renal outcomes in diabetic patients. There is also emerging evidence in non-diabetic patients. This review was conducted to analyse the renal outcomes of SGLT2i in patients without diabetes mellitus (DM). Methods: A systematic review was performed in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant manner. We included only randomized trials that examined the effect of SGLT2i on renal outcomes in non-diabetic patients. Results: A total of ten randomized trials were included with a combined cohort of 26 298 patients. There was a tendency for lesser risk of adverse renal outcomes in heart failure (HF) patients with reduced ejection fraction (EF) (hazard ratio (HR) 0.50-0.71). Lesser effect on adverse renal outcomes was seen in HF patients with preserved EF (HR 0.95). For both preserved and reduced EF HF, there was a statistically significant reduction in the rate of decline in estimated glomerular filtration rate (eGFR) (p&lt;0.001). On a short follow-up, there was a significant reversible reduction in GFR. In the long term, chronic kidney disease (CKD) proteinuric patients had a statistically significant lesser risk of adverse renal outcomes (p&lt;0.001) and a significant reduction in albuminuria (p=0.0016). CKD patients, including non-proteinuric, had a significant reduction in the rate of kidney disease progression (HR = 0.71). Conclusion: Treatment with SGLT2i significantly reduces the rate of kidney disease progression in CKD non-diabetic patients with eGFR ≥ 20 mL/min/1.73 m2. Benefit seems greater in proteinuric patients. Benefit for eGFR &lt; 20 mL/min/1.73 m2, dialysis and kidney transplant patients is yet to be defined.

Comparison of Renal Functions Evaluated by Measured Glomerular Filtration Rate in Patients Treated With Cisplatin, Carboplatin, and Oxaliplatin.

In cancer chemotherapy platinum drugs do cause damage to the normal cells and as a result, many physiological functions are derailed. Renal function as measured by measured glomerular filtration rate(mGFR) plays a large role in drug dosing on the basis of the maximum tolerated dose, which is the highest dose that may be administered without unacceptable toxicity, to maximize anticancer efficacy. The objective of the study was to compare the toxic effect of platinum drugs on renal function as measured by mGFR in patients with malignancy and to study the difference in the magnitude of nephrotoxicity by these drugs. The study was conducted in the Department of Physiology in close collaboration with the Department of Radiotherapy at a tertiary care centre in Western Rajasthan, India. 150 patients suffering from different malignances undergoing treatment with cisplatin, carboplatin, and oxaliplatin were examined for their renal functionas measured by mGFR using 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) and were compared with 50 subjects of control group. In the cisplatin group there was a gradual fall of GFR from 85.49 ml/min/1.73sqm to 58.09ml/min/1.73sqm at cycle II. In the carboplatin group it was 84.86ml/min/1.73sqm at baseline whereas cycle II was 75.5 ml/min/1.73sqm with SD ± 16.49. mGFR fell significantly (p<0.0001) in cisplatin and carboplatin groups but not in the cohort of patients who received oxaliplatin. The GFR reduction continued from the baseline to cycle I and then cycle II in cisplatin and carboplatin groups. Nephrotoxicity is a major side effectof platin drugs and further studies should be done to establish their optimal dose in relation to renal function and minimize toxicity by trying various cytoprotective agents.

A diagnostic criterion for the dynamics of chronic kidney disease in patients with diabetes

Aim to develop and clinically substantiate an objective quantitative diagnostic criterion for the dynamics of chronic kidney disease (CKD) in patients with diabetes mellitus (DM).&#x0D; Material and methods. A comparative cross-observational study of clinical indicators was performed in a general sample of patients with type 2 diabetes, divided into groups according to the parameter "GFR reduction index (RI_GFR)", which characterizes the dynamics of CKD and the development of cardiorenal syndrome in patients with diabetes. 150 protocols of outpatient consultations were selected using the compliance criteria, including the data on 72 clinical indices. The threshold value for dividing the groups of "slow" and "fast" progression of CKD according to the RI_GFR parameter was 4.21 ml/min/1.73 m2. By the method of correlation analysis, the strength of the interrelations of clinical indicators was determined, the Student's t-test and one-factor analysis of variance were used to compare the mean values of independent variables.&#x0D; Results. To quantify the dynamics of the progression of CKD in DM patients, a diagnostic parameter RI_GFR was proposed, calculated according to the original formula based on the value of GFR and the duration of the disease of DM. When assessing the statistical relationships between RI_GFR and clinical indicators, the significance of correlations with creatinine levels, duration of diabetes, insulin therapy, age, history of acute myocardial infarction, dosage of sulfonylureas, as well as the absence of correlation with indicators of achievement of glycemic control goals was noted. When dividing the sample into groups according to the rate of progression of CKD, significant differences were found in the parameters of the duration of DM disease and the use of insulin therapy, the total dose of insulin, the level of glycemia, and body mass index. Insufficient level of reliability was found in the parameters of the dosage of sulfonylureas and age.&#x0D; Conclusion. The developed original diagnostic parameter RI_GFR allows us to give an objective characteristic of the dynamics of CKD in patients with DM. A statistically significant correlation was found between the rate of progression of diabetic kidney damage and cardiovascular risk factors with less influence of the glycemic control factor at the stage of formation of cardiorenal syndrome. To clarify the influence of hemodynamic and glycemic factors on the development of cardiorenal syndrome, it is necessary to continue the study using the logistic regression analysis.

Lrpap1 (RAP) Inhibits Proximal Tubule Clathrin Mediated and Clathrin Independent Endocytosis, Ameliorating Renal Aminoglycoside Nephrotoxicity.

Proximal tubules are exposed to many exogenous and endogenous nephrotoxins that pass through the glomerular filter. This includes many small molecules such as aminoglycoside and myeloma light chains. These filtered molecules are rapidly endocytosed by the proximal tubules and lead to nephrotoxicity. To investigate whether inhibition of proximal tubule uptake of filtered toxins can reduce toxicity we evaluated the ability of Lrpap1 or RAP to prevent proximal tubule endocytosis. Munich Wistar Frömter rats were used since both glomerular filtration and proximal tubule uptake can be quantified. The injury model chosen was the well-established gentamicin induced toxicity which leads to significant reductions in GFR and serum creatinine increases. Chronic kidney disease was induced with a right uninephrectomy and left 40 minute pedicle clamp. Rats had eight weeks to recover and to stabilize GFR and proteinuria. Multiphoton microscopy was used to evaluate endocytosis in vivo and serum creatinine and 24 hour creatinine clearances were used to evaluate kidney functional changes. Studies showed preadministration of RAP significantly inhibited both albumin and dextran endocytosis in outer cortical proximal tubules. Importantly, this inhibition was found to be rapidly reversible with time. RAP was also found to be an excellent inhibitor of proximal tubule gentamicin endocytosis. Lastly, gentamicin administration for 6 days resulted in significant elevation of serum creatinine in vehicle treated rats but not those receiving daily infusion of RAP prior to gentamicin. This study provides a model for the potential use of RAP to prevent, in a reversible manner, proximal tubule endocytosis of potential nephrotoxins thus protecting the kidney from damage.

Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

Background and aimsRenal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. Methods and resultsWe observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. ConclusionsOur findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.