Median Serum Creatinine Research Articles

MO147: Fat Check: Lipid Abnormalities in Nephrotic Primary Glomerulopathies

Abstract BACKGROUND AND AIMS Lipid abnormalities are a defining feature of nephrotic syndrome. In nephrotic patients, changes such as increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) as well as decreased HDL-C: TC ratio are more frequently found than in healthy subjects. The aims of this study were to evaluate the differences in the serum lipidic profile at baseline (diagnosis) among each primary glomerulopathies (PG) presenting with nephrotic syndrome (NS) and its association with several clinical parameters such as serum albumin (SAbl) and proteinuria. METHOD We conducted a retrospective cohort study with patients older than 18 years who presented with nephrotic syndrome and diagnosed with a PG by kidney biopsy in the last 10 years in a tertiary-level hospital. RESULTS The study included 60 patients: 38 were male (63.3%), with median age of 52 (IQR 27) years, 43.3% had hypertension, median serum creatinine (SCr) was 1.11 mg/dL (IQR 0.86), median protein-creatinine ratio was 7443 (IQR 5033.5) mg/g and median SAlb of 2.0 (IQR 1.03) mg/dL. At baseline, the median TC was 320.5 mg/dL (IQR 184.5), HDL-C 55 (IQR 25.5) mg/dL, LDL-C 225mg/dL (IQR 174), TG 176 (IQR 122.6) mg/dL and HDL: TC ratio 0.19 (IQR 0.13). Median follow-up time was 24 (IQR 51) months. Patients were grouped in four categories regarding the PG subtype: membranous nephropathy (MN, 38.3%), minimal change disease (MCD, 38.3%), IgA nephropathy (IgAN, 11.7%) and focal segmental glomerulosclerosis (FSGS, 11.7%). Evaluating all the patients enrolled, we found a strong negative correlation between SAlb and TC (r = –0.511, P < .001), LDL-C (r = –0.529, P < .001) and a weaker negative correlation with TG (r = –0.282, P = .030), but not with HDL-C. We did not find a statistically significant correlation between proteinuria and each cholesterol subtype or TG levels. A Kruskal–Wallis test showed that different subtypes of PG were associated with different median HDL-C (H(3) = 12.073, P = .007) and TG serum levels (H(3) = 10.128, P = .018). No statistically significant differences in the TC, LDL-C or HDL-C: TC ratio were found. Comparing all pairs of groups, we found that HDL-C levels were statistically different between MN and MCD (45.5 versus 67 mg/dL, P < .001), but not in the other pairs. The same analysis found that TG serum levels were only significantly different between IgAN and MN (114 versus 187 mg/dL, P = .008) and between IgAN and FSGS (114 versus 200 mg/dL, P = .012). MN patients that progressed to CKD stage 5D had lower median HDL-C levels at diagnosis, when compared to the patients who did not progress (41 versus 49 mg/dL, P = .037). This difference was not observed in IgA, FSGS or MCD. CONCLUSION Each GP subtype presents a different lipid profile, particularly differing on HDL and TG. Patients with MCD presented with the highest levels of HDL-C, while MN with the lowest. Regarding TG levels, FSGS presented with the highest levels while IgAN presented with the lowest. In the membranous nephropathy group, patients that progressed to ESRD had statistically significantly lower serum levels of HDL-C. As expected, SAlb is significantly associated with TC, LDL-C and TG levels, in nephrotic patients. This could be due to different levels of lecithin–cholesterol acyltransferase (an enzyme responsible for the maturation of HDL), which is increasingly lost through urine in nephrotic syndromes. The differences found in the lipidic profile between PG subtypes could have screening, therapeutic and prognosis implications in the management of cardiovascular risk in these patients. More studies are needed to understand the pathophysiology and the prognosis significance of each lipid profile.

MO377: Correlation Between 24-H Proteinuria and Spot Urine Albumin-Creatinine Ratio in Biopsy-Proven Glomerular Diseases

Abstract BACKGROUND AND AIMS The gold standard for measurement of protein excretion is a 24-h urine collection. However, due to the cumbersome nature as well as the frequent errors in sample collection, it has been suggested that the measurement of albumin-creatinine ratio (ACR) in a spot urine sample could replace 24-h proteinuria as a valid method for the diagnosis and follow-up of renal disease, which is supported by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to assess the correlation between 24-h proteinuria and spot urine ACR in patients with biopsy-proven glomerulonephritis, METHOD We identified patients with biopsy-proven glomerular diseases who were evaluated during their disease course at our center between 1 January 2005 and 31 December 2021, and included patients with paired 24 h and spot urine samples simultaneously collected at the same day. We excluded patients with interstitial or vascular causes for kidney disease. We contrasted correlation of ACR and 24 h proteinuria according to demographic data, glomerular filtration rate measured at the day of urine collection, and type of glomerular disease. RESULTS A total of 977 paired 24-hr proteinuria and spot urine ACR samples were collected at the same day from 370 patients and included in this study. The mean age of the selected population was 52.1 ± 17.7 years, with a median serum creatinine of 1.26 mg/dL (IQR: 0.94–1.74) and mean eGFR measured by CKD-EPI of 62.4 ± 30.1 mL/min. Median 24-h proteinuria was 1.48 g/day (IQR: 0.59–3.39), and the median ACR was 539 mg/g (IQR: 131–1569). We found an excellent correlation between ACR and 24-h proteinuria (Spearman's r = 0.86, P < 0.001). This correlation was reproducible across all CKD stages, and remained strong even in patients with eGFR <30 mL/min/1.73 m2 (Spearman's r = 0.85, P < 0.001). On the other hand, after stratifying the cohort according to grade of proteinuria, we found that correlation was significantly weaker when proteinuria >3 g/day (Spearman's r = 0.50, P < 0.001) compared with lower grade proteinuria <3 g/day (r = 0.79, P < 0.001). We found no differences in correlation between ACR and 24-h proteinuria according to the type of glomerular disease, with excellent correlation across all glomerulonephritides. ROC analysis showed that a ACR cutoff of >250 mg/g was the best predictor for 24-h proteinuria >1 g/day, with an area under the curve (AUC) of 0.933, sensitivity 91% and specificity 81%, while an ACR cutoff of >800 mg/g best predicted a 24-hour proteinuria of >3.5 g/day, with an AUC of 0.922, sensitivity of 92% and specificity of 76%. CONCLUSION There is an excellent correlation between ACR and 24-h proteinuria in patients with proteinuria <3 g/day independent from eGFR and without significant variation according to the type of glomerular disease. In patients with proteinuria >3 g/day, ACR correlates poorly with proteinuria. We suggest that patients with higher grade proteinuria should always be assessed with a 24-h urine sample protein excretion for therapeutic decisions and follow-up in glomerular diseases.

MO357: Nephrology Consultation to Improve Acute Kidney Injury Outcome on General Wards

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) affects up to one in five hospitalized patients and is independently associated with high morbidity and mortality. Additionally, patients have an increased risk for developing chronic kidney disease (CKD) after AKI. The combined impact of short- and long-term consequences and the high incidence of AKI results in a significant financial burden. Adequate intervention and follow-up might reduce the clinical impact of AKI, however the evidence for this remains inconclusive. The aim of this prospective cohort study was to evaluate whether nephrology consultation had an impact on patient follow-up and clinical outcome after AKI. METHOD All patients, admitted to VU medical centre in Amsterdam between October 2018 and April 2019, were screened for AKI by an automatic warning system integrated into the hospital's electronic patient record. This warning system sent a signal if serum creatinine would rise >27 µmol/L in 48 h or increased by a factor of at least 1.5 within 7 days (KDIGO criteria for AKI). The nephrology or internal medicine resident would then assess eligibility. Exclusion criteria were: a rise in serum creatinine that did not represent an actual AKI, admittance to the intensive care unit at the time of the signal, admission for kidney transplantation and patients that died before consultation was possible. After identification, nephrology consultation was provided. For the least severe AKI cases (KDIGO stage 1), this was done by telephone after review of the patient record, and for severe AKI cases (KDIGO stage 2 and 3) by full clinical review. Patients were grouped according to adherence (consult or no consult) to this protocol. Adequate follow-up was defined as a specific post-AKI referral to a nephrologist or general practitioner after hospital discharge. Recovery of serum creatinine and 6-month mortality were used as primary measures of clinical outcome. RESULTS A total of 371 cases of possible AKI were identified by the warning system. Of those case, 218 cases were eligible for inclusion. In 160 cases, nephrology consultation was performed (consult group). In 58 cases, there was no consult (no-consult group). The average age was 67.4 years. The consult and no-consult groups were similar at baseline (mean age, male/female, incidence of hypertension and diabetes), besides a higher incidence of CKD in the consult group (79% versus 64%; P = 0.034). The consult group had a significantly larger percentage of severe AKI cases (stage 2 or 3 in 29.4% of cases versus 12.1%; P = 0.021). Treatment was initiated in 93.1% of consult cases and in 70.6% of no-consult cases (P < 0.001) and there was a more profound decrease in the serum creatinine level from peak till 6 months (–33.7% versus –19.4%; P = 0.033)). All-cause mortality (34.1% versus 27.6%; P = 0.510), post-AKI follow-up (83% versus 73.2%; P = 0.116) and median serum creatinine value at six months (119 µmol/L versus 100 µmol/L; P = 0.334) did not differ between the consult and no-consult group. A 6-month serum creatinine was only available for 50% of cases in both groups. CONCLUSION When compared with cases of generally less severe AKI in which nephrology consultation was not performed, cases with nephrology consultation were associated with higher rates of treatment of AKI, faster recovery of kidney function and similar mortality. The data are in line with earlier non-randomized research which concluded that nephrology consultation can be linked to improved outcome in AKI. Before any definitive conclusions can be drawn, these associations should be found replicable in a randomized multi-centre setting and cost-effectiveness and feasibility should be analysed.

MO541: Secondary Hyperparathyroidism Influence on Parathyroid Hormone Levels After Kidney Transplantation

Abstract BACKGROUND AND AIMS Optimal parathyroid hormone (PTH) control in patients before kidney transplantation (KT) might decrease the subsequent risk of parathyroid hyperplasia and hyperparathyroidism (HPT) after surgery. We evaluated the patient characteristics and HPT markers control before and over the first post-transplant year. METHOD We studied 210 patients (107 women, 103 men and age 45 ± 9 years) with end-stage renal failure (ESRF). All patients underwent primary KT. The duration of the pre-transplant period ranged from 0 to 158 months (median 19). The determination of HPT markers was carried out before 3 and 12 months after KT. The target PTH after KT was considered to be 130 pg/mL. Serum concentrations of PTH, calcium, phosphorus, total alkaline phosphatase activity, albumin and creatinine were determined using standard methods, estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula and stratification of chronic kidney disease stages was carried out according to the eGFR. RESULTS Patients were divided into two groups based on PTH before KT. In the first group were 63 patients with PTH > 585 pg/mL (median 866, Q1–Q3: 667; 1078), in the second group there were 147 patients with PTH 130–585 pg/mL (median 300, Q1–Q3: 225; 400). Patients with secondary HPT versus target PTH group had long duration of dialysis therapy (27 months versus 15 months; P = 0.005), frequency of hyperphosphatemia (87% versus 57%; P < 0.001) and increased activity of blood alkaline phosphatase (21% versus 4%; P < 0.001). Initial renal transplant function was the same in both groups: acute tubular necrosis amounted to 57% and 46% respectively (P = 0.07), duration of acute tubular necrosis 2 and 0 days respectively (P = 0.087). Three months after kidney transplantation in the first group median blood PTH decreased to 247 pg/mL (Q1–Q3: 163; 452), the prevalence of PTH > 130 pg/mL had 88% patients, in the second group median blood PTH decreased to 150 pg/mL (Q1–Q3: 120; 210), the prevalence of PTH > 130 pg/mL had 59% patients (P < 0.001). Hypercalcemia was in 13% patients of first group and 0 in second group (P < 0.001). Serum creatinine and eGFR did not differ and amounted respectively to 114 (Q1–Q3: 86; 150) and 110 (Q1–Q3: 80; 136) μmol/L (ns), 60 (Q1–Q3: 45; 80) and 60 (Q1–Q3: 49; 80) mL/min (ns). The ratio of stages of chronic kidney disease was the same (Figure 1). A total of 12 months after KT the blood level PTH was 180 (Q1–Q3: 95; 247) and 106 (Q1–Q3: 88; 125) pg/mL (P = 0.004), the prevalence of PTH > 130 pg/mL had 54% and 15% (P < 0.001) patients respectively. Kidney transplant function did not differ as well as after 3 months (median serum creatinine 120–121 μmol/L, eGFR 55 and 55 mL/min). In the post-transplant period, patients of the first group were more often prescribed vitamin D preparations and its analogues, five were treated with cinacalcet due to hypercalcemia and seven underwent parathyroidectomy after 1.5–2.5 years. CONCLUSION Secondary HPT before KT predicted a higher PTH level in the first year after surgery. Patients with ESRF who are on the waiting list for KT need careful monitoring of blood PTH and adequate treatment of secondary HPT.

FC 115: Long-Term Outcomes in Eculizumab-Treated Kidney Transplant Patients Enrolled in the Global Atypical Haemolytic Uraemic Syndrome Registry

Abstract BACKGROUND AND AIMS The global atypical haemolytic uraemic syndrome (aHUS) registry (NCT01522183), the largest repository of real-world data on patients with aHUS, provides key insights into disease course, natural history, and patient (pt) outcomes with and without complement inhibitor therapy. Prior to eculizumab availability, pts with aHUS had a reportedly high risk of disease recurrence and graft loss following a kidney transplant (KTx). We report the long-term clinical outcomes of eculizumab-treated pts who received a KTx. METHOD This analysis included pts enrolled from April 2012–November 2021. Pts were included in a long-term treatment outcomes study if they had ever been treated with eculizumab and were excluded if they had DGKE mutations or their diagnosis was later revised to any condition other than aHUS. The current analysis set included pts who had received a KTx no more than 30 days prior to eculizumab start or up to 60 days post eculizumab start date, had ≥3 years of follow-up (FU) post-transplant and had serum creatinine (SCr) measurements at baseline (BL) and post 3 years FU. Changes in kidney function, haematological parameters and clinical characteristics at last follow-up (LFU) were assessed. RESULTS A total of 329/1970 adult and paediatric registry pts met the inclusion criteria and received a KTx; 78 pts from 12 countries met sub-group inclusion criteria. BL demographics are shown in Table 1. Mean (SD) treatment duration was 5.7 (2.4) years and 47 (60%) pts had pathogenic genetic variants. Lab parameters at BL (closest measurement at or following KTx) and LFU are reported in Table 2. Despite large ranges, median SCr levels remained stable at LFU. Median eGFR and platelet levels were similar at BL and LFU, while lower median lactose dehydrogenase levels were seen at LFU. At LFU: four pts (5%)—three adult—had subsequent KTx(s); eight (10%)—seven adults—had received dialysis by last observation; and two (3%) had received plasma exchange/infusion. Two pts (3%) died during the observation period. CONCLUSION This study assessed a large, real-world population of pts at high risk of KTx failure. Lab parameters suggest most pts benefitted from eculizumab treatment, with few TMA-related complications and stable kidney function and haematological parameters for ≥3 years. Overall, the proportions of female pts and of pts with pathogenic genetic variants were consistent with previous studies. A potential study limitation was the relatively stringent sub-population-specific inclusion criteria. However, these data further demonstrate the beneficial impact of eculizumab treatment in the long-term management of aHUS in pts requiring KTx.

Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI.

Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI. We hypothesized that there is poor concordance between the presence of MBGC and FENa in ATI. We conducted a prospective observational study in patients with AKI seen during inpatient consultation. We extracted patients who underwent assessment of percentage of low power fields (LPFs) with MBGC by MicrExUrSed and concomitant measurement of FENa. Diagnostic concordance between MBGC and FENa and their individual prognostic value were examined. Our cohort included 270 patients, 111 (41%) of whom were women. Median age was 61 years (range 27-92 years), and median serum creatinine was 3.7 mg/dl ( range1.2-22.0 mg/dl). MBGC were found in 49% (133/270). FENa <1% (inconsistent with ATI) was found in 50/133 (38%), 38/115 (33%), and 16/45 (36%) of those with >0%, ≥10%, and ≥50% LPFs with MBGC, respectively. Concordance between FENa and MBGC for ATI diagnosis was deemed fair (estimated κ-coefficient=0.2), and poor (κ=-0.11) within a subgroup of patients with preexisting chronic kidney disease (n=139). In patients with biopsy-proven ATI (n=49), MBGC had 100% specificity and 100% positive predictive value for ATI. MBGC were associated with greater risk for ≥50% increase in creatinine from baseline at discharge (acute kidney disease [AKD]). About two of five patients with MBGC identified by MicrExUrSed presented with FENa <1%. Presence of MBGC was consistent with ATI, as verified by biopsy, and were predictive of AKD. These data suggest that the sole reliance in low FENa to exclude ATI should be abandoned, and MicrExUrSed should be pursued for AKI diagnosis.

P238 Pre-pregnancy switching from mycophenolate to azathioprine in patients with lupus nephritis: a retrospective outcome analysis

Abstract Background/Aims Mycophenolate mofetil is not recommended in pregnancy due to teratogenic effects. A previous small prospective study found that switching from MMF to AZA rarely led to renal flares. Our aim was to assess the impact of switching from MMF to AZA on renal flares and pregnancy outcomes in a lupus nephritis cohort. Methods A retrospective analysis of the records of patients attending the renal and antenatal clinics at St Thomas’s Hospital in London who underwent pre-pregnancy counselling and switched from MMF to AZA was undertaken between January 2019 and December 2020. Inclusion criteria included a diagnosis of SLE based on the 2019 EULAR/ACR classification criteria for SLE and lupus nephritis assessed by a biopsy and classified according to the International Society of Nephrology/Renal Pathology Society 2003 classification. A flare was defined as rising urine PCR, decreasing serum albumin, decreasing serum complement and rising dsDNA antibodies and/or an increase in serum creatinine. Analyses included descriptive statistics [mean (standard deviation) and median (interquartile ranges) for continuous variables and frequency (percent) for categorical values]. Results Twenty-seven patients were included in this study. 55% were of Afro-Caribbean or Asian background and remaining were Caucasian. The median age at SLE diagnosis was 22 (18-26) years. The average disease duration prior to treatment switch was 8 years. The median time between biopsy and switching was 32 months (17-69). 25.9% of patients had a diagnosis of APS. 48% were Ro positive, while 85.2% were positive for dsDNA antibodies. The median serum creatinine was 69 umol/L (58-84), median serum albumin was 42g/L (38-47) and median PCR was 26.5mg/mol (12-61) prior to switching. Our study showed that nine patients (33.3%) flared after switching. five patients (18.5%) flared during pregnancy. 10 (37%) patients went onto have successful pregnancies, two (7.4%) had miscarriages, three (11.1%) patients developed preeclampsia. 46% of patients with class III/IV Nephritis on biopsy developed complications in pregnancy. 36% of patients with dsDNA had poor pregnancy outcomes compared to 25% who were dsDNA negative. 42.2% of patients of Afro-Caribbean/Asian background flared during pregnancy compared to 25% of their Caucasian counterparts. Conclusion Although azathioprine is an option in patients with lupus nephritis who are planning pregnancy, there is a need to identify patients at risk of a disease flare on switching from MMF. This study showed that patients with low serum albumin, creatinine &amp;gt;65, urine PCR &amp;gt;50 and positive dsDNA antibodies at the time of the switch were more likely to flare after switching and in pregnancy. Disclosure S.S. Ali: None. S. Sangle: None. D. D'Cruz: None.

Outcomes in Smaller Body Size Adults After HeartMate 3 Left Ventricular Assist Device Implantation

BackgroundOutcomes in patients with smaller body size after HeartMate 3 left ventricular assist device (HM3) implantation are not well characterized. We sought to evaluate outcomes in smaller vs larger body surface area (BSA) patients in the MOMENTUM 3 pivotal trial and its Continued Access Protocol cohort. MethodsThe analysis cohort included 1015 HM3 patients divided into 2 groups: BSA ≤1.70 m2 (small patients, n = 82) and BSA >1.70 m2 (large patients, n = 933). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or to remove a malfunctioning device. Adverse events were compared between groups. ResultsSmaller patients were more frequently women (56.1% vs 17.7%; P < .001) and had lower prevalence of diabetes (28.1% vs 43.9%; P = .005) and hypertension (51.2% vs 71.9%; P < .001), larger median indexed LVEDD (normalized by BSA, 40 vs 33 mm/m2; P < .001), and lower median serum creatinine concentration (1.1 vs 1.3 mg/dL; P < .001). The proportion of patients achieving the composite end point at 2 years was 77% in both groups (adjusted hazard ratio, 1.14; 95% CI, 0.68-1.91; P = .62). Two-year adverse event rates were also similar between groups except for sepsis (6.1% vs 14.9%; P = .029) and cardiac arrhythmias (24.4% vs 35.3%; P = .005), which were higher in the larger patients. ConclusionsOutcomes after HM3 implantation were comparable between small and large patients. Smaller body size should not be used to deny HM3 implantation in patients who are otherwise suitable candidates for durable mechanical circulatory support.

Associations between physical activity levels and renal recovery following acute kidney injury stage 3: a feasibility study

BackgroundAcute kidney injury (AKI) can lead to chronic kidney disease, which results in poor long-term outcomes. There is plausibility that increased levels of physical activity may promote renal recovery post-AKI. This study aimed to investigate associations between physical activity levels and renal recovery following stage 3 AKI, and to assess the feasibility of measuring physical activity levels in this population.MethodsForty One hospitalised patients with AKI stage 3 were enrolled. Serum creatinine and estimated glomerular filtration rate (eGFR) were collected at 12 months prior to the development of AKI, during the hospital admission when the episode of AKI stage 3 occurred, and at 1-, 3- and 6-months post discharge. All participants completed the General Practice Activity Questionnaire (GPPAQ) to assess physical activity levels. A pedometer was also worn for 7 days immediately following discharge and at 6-months post discharge to ascertain an average daily step count. Feasibility outcomes including eligibility, recruitment and retention rates, and losses to follow up were also assessed.ResultsThe average (± SD) baseline eGFR and median (IQR) serum creatinine was 71 ± 20 mL/min/1.73m2 and 85 (49) μmol/L respectively. A threefold increase in creatinine occurred during hospitalisation 436 (265) μmol/L. Greatest renal recovery occurred prior to discharge, with recovery continuing for a further three months. Inactive individuals (low GPPAQ scores) had consistently higher serum creatinine values compared to those who were active: 1 months 122 (111) μmol/L vs 70 (0) μmol/L, 6 months 112 (57) μmol/L vs 68 (0) μmol/L. Individuals with higher step counts also displayed better renal recovery 6-months post discharge (r = -0.600, p = 0.208).ConclusionsHigher levels of physical activity are associated with improved renal recovery after 6- months following an episode of stage 3 AKI. A future randomised controlled trial is feasible and would be required to confirm these initial findings.

Predictors of Peripheral Artery Disease Progression. Is there Any Role for Vascular Age?

Predictors of Peripheral Artery Disease Progression. Is there Any Role for Vascular Age?

Anti-neutrophil cytoplasmic antibody seropositivity in young adults aged up to 35 years: kidney histopathological findings and patient outcomes

ObjectiveTo investigate the clinical features, pathological renal findings, and outcomes in young adults with anti-neutrophil cytoplasmic antibody (ANCA) seropositivity.MethodsAdults aged ≤35 years, with ANCA seropositivity, who underwent renal biopsy and received treatment comprising a combination of corticosteroids and cyclophosphamide between January 2004 and May 2018, were retrospectively enrolled.ResultsThirteen patients with ANCA seropositivity were included, all of whom presented with kidney disease at diagnosis: 10 (76.9%) with ANCA-associated pauci-immune glomerulonephritis, one with ANCA-associated crescentic glomerulonephritis with immune complex deposition, one with immunoglobulin A nephropathy, and one with membranous nephropathy. The median serum creatinine level was 183.2 μmol/l (range, 55.0–1024.0 μmol/l). Respiratory symptoms (9/13 [69.2%]) and nonspecific gastrointestinal symptoms (5/13 [38.5%]) were the most common extrarenal manifestations. Remission was achieved in 10 (91%) of 11 ANCA-associated nephritis cases, and median interval from diagnosis to relapse was 30 months (range, 9–63 months). Cumulative relapse-free survival rates at 1 and 5 years were 100% and 88.9%, respectively. Overall, 1-year and 5-year renal survival rates were 80.8% and 58.9%, respectively.ConclusionRenal histopathology varied in young adults with ANCA seropositivity. Although relapse rates in this young adult population were generally low, long-term renal survival rates remain unsatisfactory.

Donor-derived cell-free DNA and renal allograft rejection in surveillance biopsies and indication biopsies.

To evaluate the role of circulating dd-cfDNA in allograft surveillance in immunologically high-risk patients, a retrospective cross-sectional study of 261 kidney transplant recipients who underwent outpatient allograft biopsy at our center between September 2020 and August 2021 was performed. Of the 236 dd-cfDNA results included, 37 samples were obtained at the time of a surveillance biopsy in sensitized recipients and 199 at the time of a clinically indicated biopsy. The median serum creatinine at the time of the biopsy was 1.3mg/dl and 2.1mg/dl for surveillance biopsies and clinically indicated biopsies, respectively (P<.001). Rejection was diagnosed in 27% of surveillance biopsies and 29% of clinically indicated biopsies. Among surveillance biopsies, sensitivity and specificity to detect rejection were 0% and 89%, respectively, and among clinically indicated biopsies they were 28% and 96%, respectively. The sensitivity and specificity to detect antibody-mediated rejection were 0% and 91% among surveillance biopsies and 50% and 94% among clinically indicated biopsies. Nine biopsies without rejection findings had corresponding dd-cfDNA of ≥1%. Our data does not support dd-cfDNA as a biomarker for kidney allograft rejection, even in immunologically high-risk patients in the absence of graft dysfunction.

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy

IntroductionAnticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed.MethodsRetrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed.ResultsA total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis.ConclusionIgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Management of acute kidney injury in frail patients with biopsy-proven cast nephropathy: a combined approach with chemotherapy plus Supra-hemodiafiltration with post-adsorption endogenous reinfusion.

Patients with multiple myeloma often have kidney involvement with acute kidney injury which is frequently due to cast nephropathy. Hemodiafiltration with endogenous reinfusion (HFR) allows removal from the circulation of significant amounts of free light chains (FLCs) responsible for tubular damage. Between 2014 and 2018, 13 patients affected bymultiple myeloma (64% λ chain and 36% k), including 10 caseswith biopsy-proven cast nephropathy, were treated with this technique. Each patient had high free light chains levelsat diagnosis: median 8586mg/l for λ and 4200mg/l for k, and stage III acute kidney injury (median serum creatinine 7.5mg/dl). We initially performed daily HFR-Supra sessions and then modulated them based on renal response (mean 10 sessions/patient). At the same time, the patients also received various chemotherapy regimens, depending on their hematological criteria. Forty-six percentof patients showed at least partialrenal functionrecovery within the third month, thus allowing dialysis discontinuation; 38% remained on dialysis. Two patients died. The mean reduction rate offree light chains at the end of the HFR-Supra cycle was 85% (k) and 40% (λ), respectively. Serum albumin remained stable during the whole treatment. In our experience, the synergistic effect of chemotherapy and HFR-Supra led to a recovery of renal function in 6 out of 13 patients presenting with severe dialysis-requiringacute kidney injury. HFR-Supraallowedstable albumin levels, withhigh free light chains removal rate, at arelatively low costs.

Experience with the use of mohan's valvotome for posterior urethral valve ablation at a centre in North-Eastern Nigeria.

Introduction:Posterior urethral valve (PUV) is the most common congenital cause of lower urinary tract obstruction in boys. Management has remained challenging in our region, with features of renal impairment evident in some patients at the time of presentation. Endoscopic valve ablation is the gold standard of treatment, but this is not readily available in our setting. Mohan's valvotome has been described as an alternative device for valve ablation. This study aimed to highlight the clinical presentation, management and early outcomes following valve ablation using Mohan's valvotome.Methods:A retrospective study of boys with PUVs managed between September 2014 and June 2018 was done. The demographic characteristics, clinical features, investigations, treatment and initial outcomes were reviewed. The main outcome measures were improved post-ablation urinary stream, serial serum creatinine values at presentation, 4–5 days of initial catheter drainage and at follow-up.Results:There were ten boys with the median age at presentation of 4 months (mean: 23.9 months; range 10 days to 7 years). Four patients presented after 1 year. All the patients had features of bladder outlet obstruction with associated fever in seven patients and urinary tract infections in six patients. Nine patients (90%) had suprapubic masses, while 2 had ballotable kidneys with co-existing urinary ascites in one patient. Valve ablation was achieved with Mohan's valvotome. There was a significant improvement in the urine stream in all patients. The median duration of follow-up was 7.5 months. Median serum creatinine was 0.95 mg/dl (mean 0.94 mg/d ± 0.38 mg/dl) at follow-up, compared to a median of 4.03 mg/dl at presentation (P = 0.01).Conclusion:Initial drainage and definitive valve ablation with Mohan's valvotome is associated with improved serum creatinine and urinary stream.

Association of ultrasonographic features with histologic findings in 71 dogs with protein-losing nephropathy (2008-2018).

To determine whether ultrasonographic features in dogs with protein-losing nephropathy (PLN) were associated with renal biopsy findings and compare corticomedullary ratios between dogs with PLN versus non-renal disease. 71 dogs with PLN and 33 dogs without renal disease. Medical records and archived ultrasonographic images for dogs with PLN that underwent renal biopsy between 2008 and 2018 were reviewed. Corticomedullary ratios were measured. In dogs with PLN, median serum creatinine and BUN concentrations and urine-protein-to-creatinine-ratio prior to renal biopsy were 3.4 mg/dL (interquartile range [IQR], 1.2 to 5.3 mg/dL), 80 mg/dL (IQR, 28 to 105 mg/dL), and 11.4 (IQR, 6.4 to 18.3), respectively. Histologic abnormalities within the tubulointerstitial space were associated with cortical echogenicity. Gastric wall thickness > 5 mm was associated with a histologic diagnosis of acute glomerular disease. Dogs with immune complex-mediated glomerular disease were more likely to have abnormal gastric mural architecture. Other ultrasonographic features of the kidneys, liver, and stomach and the presence of ascites did not help to differentiate immune complex-mediated from non-immune complex-mediated glomerular disease, acute from chronic disease, or amyloid from non-amyloid disease or distinguish whether tubulointerstitial disease was present or absent. Median left corticomedullary ratio for 66 dogs with PLN (1.2) was significantly higher than that for the 33 dogs without renal disease (1.0). Ultrasonographic features were poorly associated with specific pathological disorders in dogs with PLN. In this study, the corticomedullary ratio was higher in dogs with PLN, indicating the presence of cortical thickening, but the clinical relevance is unknown.

Clinical and Histopathological Profile of Immunoglobulin A Nephropathy Patients in Central Part of India: A Single-Center Study.

The objective of the study was to assess clinical and histopathological profile of patients who were diagnosed as immunoglobulin A nephropathy (IgAN) on renal biopsy. Medical data were collected for this retrospective study at a single center from patients with biopsy-proven IgAN, from those biopsied between January 2017 and September 2020. A total of 347 renal biopsies were performed during the study. There were 52 patients with primary IgAN who met our inclusion criteria. Males were more commonly affected (61.5%). The mean age at the time of kidney biopsy was 35.26 ± 10.39 years. Hypertension was present in 84.5% of patients. Median serum creatinine and estimated glomerular filtration rate (eGFR) at presentation were 3.58 mg/dL and 15.8 mL/min/1.73 m2, respectively. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/ interstitial fibrosis (T1/T2), and crescents (C1/C2) were present in 46.2%, 38.5%, 88.5%, 75% and 36.6% of patients respectively. Thrombotic microangiopathy (TMA) and hypertensive vasculopathy were seen in 38.5% and 86.5% of patients respectively. The presence of tubular atrophy (T1/T2), hypertensive vasculopathy, and TMA on renal biopsy was significantly associated with low eGFR at presentation whereas no such correlation could be established with segmental glomerulosclerosis (S1), crescents (C1/C2), mesangial (M1) and endocapillary hypercellularity (E1). The presence of hypertensive vasculopathy and TMA on renal biopsy was associated with poor renal function at presentation. The most common clinical presentation of IgAN was hypertension and so we suggest patients with hypertension should be screened for microscopic dysmorphic hematuria and proteinuria, if present, should undergo a renal biopsy to diagnose this disease in early stages.

Effect of Prophylactic Dose of Trimethoprim-Sulfamethoxazole on Serum Creatinine in Japanese Patients With Connective Tissue Diseases.

Objectives:At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation.Methods:A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated.Results:A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (−0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation.Conclusions:These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL.

RENAL INVOLVEMENT IN AA AMYLOIDOSIS: A SINGLE-CENTER EXPERIENCE WITH CLINICAL AND HISTOPATHOLOGICAL DATA

Objective We aimed to evaluate clinicopathological features in patients with renal amyloid A (AA) amyloidosis to analyze the impact of renal biopsy on renal and patient outcomes. Materials and Methods We retrospectively collected data regarding baseline and follow-up clinical and laboratory features. The same pathologist scored each kidney biopsy specimen according to amyloid distrubition and amount with tubulointerstitial findings. We added all scores and obtained renal amyloid prognostic score (RAPS) and then divided patients into three RAPS grades (RAPS grade I, II, III). Results Eighteen patients (male,72.2%) with a median age of 51.5 (IQR, 45-58.3) years were included in the study. The most common disease related to AA amyloidosis was previous tuberculosis (33.3%). Median serum creatinine of patients at renal biopsy time was 1.61 (IQR, 0.91-2.89) mg/dL with a median 24-h protein excretion, 6.8 [IQR, 4.6-8.9] g/day. 100%, 94.4%, 55.6% of patients’ renal biopsies had vascular, glomerular (mostly diffuse mesangiocapillary) and interstitial amyloid depositions. RAPS grade I, II and III were detected in 5.6%, 27.8% and 66.7% of the patients, respectively. Ten patients (55.5%) reached end-stage renal disease (ESRD) at a median time of 15 (IQR, 2.3-32.3) months post-biopsy. ESRD was correlated with interstitial fibrosis/tubular atrophy (r=0.608, P=0.01). Death-censored renal survival rates at 1,3 and 5 years were 83.3%, 58.7% and 43.5%, respectively. Six patients (33.3%) died. Patient survival rates at 1,3 and 5 years were 88.9%, 69.6 and 55.7%, respectively. Conclusion Early diagnosis of AA amyloidosis with renal biopsy and scoring biopsy specimen according to amyloid distribution with other histopathological findings may be useful to manage the disease and predict the prognosis.

Diagnosis and Course of Membranous Nephropathy in Adults: Comparison by Age Group

Introduction: There have been few studies comparing younger and older adults with membranous nephropathy. The objective of this study was to compare younger and older patients with membranous nephropathy, in terms of the clinical, etiological, remission, and survival data. Method: This was a retrospective study of patients with membranous nephropathy who underwent renal biopsy between 2009 and 2017. Results: We included 214 patients with membranous nephropathy. At diagnosis, 169 (79%) of those patients were <60 years of age and 45 (21%) were ≥60 years of age. There was a predominance of males in both groups. The degree of proteinuria and the prevalence of hematuria did not differ significantly between the groups. However, the median serum creatinine level was higher in the ≥60-year group as was the prevalence of hypertension. Of the patients evaluated, 36 (16.8%) had secondary membranous nephropathy. Although the proportions of infectious and autoimmune causes were comparable between the two groups, neoplastic etiologies were more common in the ≥60-year group. A total of 86 in the <60-year group and 25 in the ≥60-year group were followed long term, and partial or complete remission was achieved in 68.5% and 68.0% of the younger and older patients, respectively. However, whom progressed to requiring dialysis eight (9.3%) were in the <60-year group patients and eight (32.0%) of the ≥60-year group patients (p = 0.0045). Conclusion: Despite having worse renal function at diagnosis, older patients with membranous nephropathy appear to have remission rates comparable to those of younger patients with the disease, which demonstrates the benefits of seeking diagnosis and treatment.