scholarly journals Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006972020
Author(s):  
Hirokazu Marumoto ◽  
Nobuo Tsuboi ◽  
Vivette D. D'Agati ◽  
Takaya Sasaki ◽  
Yusuke Okabayashi ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Kidney Biopsy ◽  
Limited Capacity ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Ckd Stage ◽  
Unenhanced Computed Tomography ◽  
Single Nephron ◽  
Volume Assessment ◽  
Clinicopathologic Findings

Background: Single nephron dynamics in progressive IgA nephropathy (IgAN) have not been studied. We applied novel methodology to explore single nephron parameters in IgAN. Methods: Non-globally sclerotic glomeruli (NSG) and globally sclerotic glomeruli (GSG) per kidney were estimated using cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Estimated single-nephron GFR (eSNGFR) and urine protein excretion (SNUPE) were calculated by dividing eGFR and UPE by the number of NSG. Associations with CKD stage and clinicopathologic findings were cross-sectionally investigated. Results: This study included 245 IgAN patients (mean age 43 y, 62% male, 45% on renin-angiotensin aldosterone system [RAAS] inhibitors pre-biopsy) evaluated at kidney biopsy. CKD stages were 10% CKD1, 43% CKD2, 19% CKD3a, 14% CKD3b and 14% CKD4-5. With advancing CKD stage, NSG decreased from mean 992,000 to 300,000 per kidney whereas GSG increased from median 64,000 to 202,000 per kidney. In multivariable models, advancing CKD stage associated with lower numbers of NSG, higher numbers of GSG, and lower numbers of GSG+NSG, indicating potential resorption of sclerosed glomeruli. In contrast to the higher mean glomerular volume and markedly elevated SNUPE in advanced CKD, the eSNGFR was largely unaffected by CKD stage. Lower SNGFR associated with Oxford scores for endocapillary hypercellularity and crescents whereas higher SNUPE associated with segmental glomerulosclerosis and tubulointerstitial scarring. Conclusions: SNUPE emerged as a sensitive biomarker of advancing IgAN. The failure of eSNGFR to increase in response to reduced number of functioning nephrons suggests limited capacity for compensatory hyperfiltration by diseased glomeruli with intrinsic lesions.

scholarly journals Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy

2016 ◽  
Vol 44 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Xinfang Xie ◽  
Jicheng Lv ◽  
Sufang Shi ◽  
Li Zhu ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Immunosuppressive Therapy ◽  
Iga Nephropathy ◽  
Severe Pneumonia ◽  
Rank Test ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Log Rank Test ◽  
Active Complement

Background: Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. Methods: Twelve patients with severe CreIgAN who received PE as addition to routine immunosuppressive therapy, followed for more than 6 months, were involved. Twelve matched historical controls who received immunosuppressive therapy alone were selected by propensity score matching. Renal survival, plasma IgA-IgG complex and active complement products were assessed. Results: Nine men and 3 women received a median of 7 PE courses (range 5-10). Their baseline urine protein excretion rate was 5.8 (4.5-8.7) g/day, and their serum creatinine level was 705.3 ± 296.4 μmol/l. During a mean follow-up of 15.6 months (6-51 months), 6 of the 12 PE group patients were free of dialysis, while all the control patients were dialysis dependent (6 of 12 vs. 0 of 12, p = 0.014). In the PE group, dialysis had to be restarted for 1 patient owing to the development of severe pneumonia and pulmonary failure. PE was associated with a higher kidney survival rate (log rank test, p = 0.026) during follow-up. It also significantly decreased plasma IgA-IgG complex levels (pre-PE: 85.3 ± 25.9% vs. post-PE: 38.4 ± 12.4%, p < 0.001) and plasma and urinary active complement product levels, including C3a, C5a and soluble C5b-9. The latter levels remained low until the last follow-up. Conclusion: This study indicated that PE could increase renal recovery rates in severe CreIgAN.

scholarly journals Leflunomide Plus Low-dose Prednisone in Patients with Progressive IgA Nephropathy: A Multicenter, Prospective, Randomized, Open-labelled and Controlled Trial

2020 ◽  
Author(s):  
Zhaohui Ni ◽  
Zhen Zhang ◽  
Zanzhe Yu ◽  
Fuming Lu ◽  
Changlin Mei ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Low Dose ◽  
Controlled Trial ◽  
Efficacy And Safety ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Risk Of Progression ◽  
The Difference ◽  
Dose Prednisone

Abstract Background: This trial was designed to assess the efficacy and safety of Leflunomide (LEF) plus low-dose prednisone for the treatment of progressive IgA nephropathy (IgAN). Methods: We did a prospective, randomized, open-labelled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at a risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF group) or conventionally accepted-dose prednisone (prednisone group). Our primary outcome was 24h urine protein excretion(UPE) and secondary outcomes were serum albumin(sALB), serum creatinine(Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. Results:108 patients (59 in LEF group, 49 in prednisone group) were enrolled and finished their treatment and follow-up periods. The difference in baseline data between the two groups was comparable. Compared with baseline, both groups showed significant decrease in 24h UPE(p<0.01) and increase in sALB (p<0.01), with stable Scr and eGFR throughout the 12-month treatment period. What’s more, these effects sustained through the 12-month follow-up period. However, there was no difference in 24h UPE, sALB, Scr and eGFR between the two groups (P>0.05). At 12 months, difference of overall response rate, relapsing rate and incidence of adverse events between the two groups was not significant. Conclusions: The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in treatment of progressive IgAN are comparable. Trial registration: The trial is registered at isrctn.org with the ISRCTN97636235 on July 28, 2006.

scholarly journals Clinical efficacy and safety of full-dose versus half-dose corticosteroids plus leflunomide for IgA nephropathy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yebei Li ◽  
Yi Xiong ◽  
Tianlun Huang ◽  
Xin Liu ◽  
Gaosi Xu
Keyword(s):  
Iga Nephropathy ◽  
Estimated Glomerular Filtration Rate ◽  
Kidney Biopsy ◽  
Full Dose ◽  
Protein Excretion ◽  
Half Dose ◽  
Dose Corticosteroid ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent. Methods A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation). Results During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group. Conclusions LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.

scholarly journals Hormone therapy and urine protein excretion

2018 ◽  
Vol 25 (6) ◽  
pp. 625-634 ◽  
Author(s):  
Andrea G. Kattah ◽  
Maria L.G. Suarez ◽  
Natasa Milic ◽  
Kejal Kantarci ◽  
Burcu Zeydan ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Urine Protein ◽  
Urine Protein Excretion ◽  
Protein Excretion

Abstract 171: Improving Adherence to Antihypertensive Agents for Hypertensive Patient With Chronic Kidney Disease

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Yunyun Li ◽  
Xianghong Zeng ◽  
Xiangji Zeng ◽  
Jiangyuan Xie
Keyword(s):  
Blood Pressure ◽  
Treatment Group ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Antihypertensive Agents ◽  
Renal Dialysis ◽  
Medication Possession Ratio ◽  
Urine Protein ◽  
Urine Protein Excretion ◽  
Protein Excretion

Background: hypertension is a modifiable and very important risk factor in chronic renal disease (CKD), and medication adherence (MA) is critical in reaching the treatment goals. Improvement of MA for antihypertensive agents and its impact on blood pressure (BP) in CKD practice settings are not well studied. Methods: In a prospective, controlled open-label studies, the authors have evaluated the four year MA for antihypertensive agents on progress of renal disease and risk of development of cardiovascular disease in 546 hypertension patients with CKD from 2006 to 2014 with targeted nurse-physician intervention. Before randomization Outpatient BP measurements were averaged as high (>140/ 90 mm Hg) . Blood pressure ,serum creatinine(Cr) and potassium were monitored every 14 days in the period of follow-up by physician and healthcare nurse so that every patient is able to perforce self-monitoring BP at home and medication possession ratio(MPR) of target systolic blood pressure<130/80 mmHg is more than 90 % in observation groups. MA was calculated using medication possession ratio (MPR = actual treatment days/total possible treatment days). Good versus Poor MA (MPR ≥ 0.9 vs. <0.9) groups were compared for differences in outcome and laboratory variables. Results: By the end of four year,MPR in observation group is 94% and in other is 38%, mean blood pressure in good MA group was 126/76±9/7 mmHg and in control was 146/88±19/12 mmHg, Cr clearance increased from 51±2.0 to 64±3.0 ml/min (p<0.001)in the group of good MA group, By contrast, Cr clearance decreased significantly from 52±1.9 to 40±3.6 ml/min( P<0.001)in the controls. During this time, urine protein excretion decreased from 1.4±0.5 to 0.7±0.4g every 24 hours(P<0.0001) in the treatment group ,but urine protein excretion decreased slightly (from 1.3±0.4 to 1.2±0.6,P>0.05)in the controls. 20 patients had got ACS ,28 patients stroke,38 patients had got pneumonia, 11 patients renal dialysis and nine patient died (6 in SCD and 2 in heart failure and 1 in pneumonia) in controls ,but six patient had stroke ,11 pneumonia, 3 patient renal dialysis and four patients died (2 in SCD and 2 in non-cardio causes) in the treatment group, but incidence of hyperkalaemia was similar between two groups. Conclusions: Good MA is associated with a greater controlled hypertension, better protection of heart and kidney and may decrease mortality than the poor MA.

scholarly journals Glomerular Immunodeposits of Patients with IgA Nephropathy Are Enriched for IgG Autoantibodies Specific for Galactose-Deficient IgA1

2019 ◽  
Vol 30 (10) ◽  
pp. 2017-2026 ◽  
Author(s):  
Dana V. Rizk ◽  
Manish K. Saha ◽  
Stacy Hall ◽  
Lea Novak ◽  
Rhubell Brown ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Iga Nephropathy ◽  
Kidney Biopsy ◽  
Immunofluorescence Microscopy ◽  
Kidney Tissue ◽  
Antigenic Specificity ◽  
Biopsy Specimens ◽  
Phospholipase A2 Receptor ◽  
Sds Page ◽  
Specific Igg

BackgroundIgA nephropathy (IgAN) is the leading primary GN worldwide. The disease is thought to result from glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1). However, routine immunofluorescence microscopy fails to detect IgG in many kidney biopsies from patients with IgAN and the specificity of IgG in immunodeposits has not been tested.MethodsWe used remnant frozen kidney-biopsy specimens from 34 patients with IgAN; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy. Six patients with primary membranous nephropathy (MN) and eight with lupus nephritis (LN) served as controls. IgG in the kidney tissue was extracted and its amount determined by ELISA. IgG molecular integrity was assessed by SDS-PAGE immunoblotting. Antigenic specificity of extracted IgG was determined by ELISA using phospholipase A2 receptor (PLA2R) or Gd-IgA1 as antigen. In addition, ten other IgAN cases, six IgG-positive and four IgG-negative by routine immunofluorescence, were used for colocalization studies by confocal microscopy.ResultsIgG extracted from MN but not IgAN immunodeposits reacted with PLA2R. Conversely, IgG extracted from IgAN but not MN or LN immunodeposits reacted with Gd-IgA1. Even IgAN kidney-biopsy specimens without IgG by routine immunofluorescence microscopy had IgG specific for Gd-IgA1. Confocal microscopy confirmed the presence of IgG in the IgAN biopsies with colocalization of glomerular IgA and IgG.ConclusionsThese results reveal for the first time that IgAN kidney biopsies, with or without IgG by routine immunofluorescence, contain Gd-IgA1–specific IgG autoantibodies. These findings support the importance of these autoantibodies in the pathogenesis of IgAN.

scholarly journals To evaluate the diagnostic value of protein: creatinine ratio in a single voided urine sample for quantitation of proteinuria compared to those of a 24-hour urine sample in patients with preeclampsia

2014 ◽  
Vol 9 (2) ◽  
pp. 45-53
Author(s):  
S Hossain ◽  
A Ghosh ◽  
A Chatterjee ◽  
G Sarkar ◽  
SS Mondal
Keyword(s):  
Urine Sample ◽  
Gold Standard ◽  
Diagnostic Value ◽  
Standard Test ◽  
Creatinine Ratio ◽  
Urine Protein ◽  
Predictive Values ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Gold Standard Test

Objective: This study was done to evaluate the diagnostic value of protein: creatinine ratio in a single voided urine sample for quantitation of proteinuria compared to those of a 24 hour urine sample in patients with preeclampsia. Methods: A prospective simple random sample study was done on the hypertensive pregnant women attending the antenatal clinic or admitted in Department of Obstetrics and Gynaecology. It included all women being evaluated for preeclampsia, regardless of the alerting sign or symptom, suspected severity or co-morbid conditions. The main measures were the urinary protein to urinary creatinine ratio by random (spot) direct measurement and the 24-h urinary protein excretion by a 24-h urine collection. The data obtained was statistically analyzed. Results: Out of the 78 patients with gestational hypertension included in our study 48 patients had significant proteinuria (e”300mg/day). Only 2 patients had proteinuria of the range of greater than 3500mg. Among the patients, 50 had a positive protein: creatinine ratio (e”0.3) while 28 patients had a negative protein: creatinine ratio (<0.3). The P: C ratio was able to correctly identify 44 out of 48 patients with significant proteinuria (when the comparison is made with the gold-standard test; i.e., 24-hour urine protein). It could also identify 24 out of 30 patients without significant proteinuria as compared to the gold-standard test. In this study, the Protein: Creatinine ratio with a sensitivity of 91.67%, a specificity of 80%, positive predictive values 88% and the negative predictive values 85.71%. Conclusions: Our data suggests that the protein: creatinine ratio in single voided urine is a highly accurate test (p value < 0.0000001) for discriminating between insignificant and significant proteinuria. Based on the above findings we conclude that a random urine protein excretion predicts the amount of 24- hour urine protein excretion with high accuracy. This could be a reasonable alternative to the 24-hour urine collection for detection of significant proteinuria in hospitalised pregnant women with suspected preeclampsia. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 45-53 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9687

PLATELET ACTIVATING FACTOR (PAF) AS A MEDIATOR OF PROTEINURIA IN ISOLATED PERFUSED KIDNEY (IPK).

1987 ◽  
Author(s):  
F Delani ◽  
M Tagliaferri ◽  
D Macconi ◽  
C Lupini ◽  
N Perico ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Sprague Dawley ◽  
Cationic Protein ◽  
Glomerular Permeability ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Sprague Dawley Rats ◽  
Vehicle Injection ◽  
Stabilization Period ◽  
Krebs Henseleit Buffer

PAF amplifies tissue damage in glomerulonephritis and can promote proteinuria stimulating platelet and neutrophil cationic protein release. We used IPK to establish whether PAF directly causes proteinuria. Kidneys were isolated from male Sprague-Dawley rats and perfused at constant pressure (100 mmHg) in a closed circuit with a Krebs-Henseleit buffer containing glucose urea creatinine, BSA (1%), Ficoll 70 (3.5%) and amino acids. After 25 min stabilization period, a basal 10 min clearance period was followed by PAF (1.8 nM f.c. n = 6) or vehicle (n = 5) injection into the renal artery. As seen in the figure PAF but not vehicle significantly (p<0.01) increased urine protein excretion. No significant changes in GFR (as creatinine clearance) were observed after PAF or vehicle injection (Basal: 0.786 ± 0.075 PAF: 0.658 ± 0.070. Basal 0.653 ± 0.081, vehicle 0.639 ± 0.074 ml/min/g kidney). The data indicate that PAF may directly increase glomerular permeability to proteins.

Treatment of Relapsed Myeloma in a Patient With Renal Insufficiency

2018 ◽  
Vol 36 (20) ◽  
pp. 2012-2016
Author(s):  
Joan Bladé ◽  
Laura Rosiñol ◽  
María Teresa Cibeira ◽  
Carlos Fernández de Larrea
Keyword(s):  
Serum Creatinine ◽  
Light Chain ◽  
Progressive Disease ◽  
M Protein ◽  
Bone Lesions ◽  
High Dose ◽  
Kappa Light Chain ◽  
Urine Protein ◽  
Urine Protein Excretion ◽  
Protein Excretion

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old man was diagnosed in March 2010 with stage III immunoglobulin G kappa multiple myeloma (MM) after presenting with bone pain as a result of multiple lytic bone lesions and T12 vertebral collapse. Laboratory work-up showed a serum M protein of 72 g/L and a 24-hour kappa light-chain urine protein excretion of 730 mg, hemoglobin of 10.2 g/dL, serum albumin of 49 g/L, serum β2-microglobulin of 6.4 mg/L, serum creatinine level of 1.6 mg/dL with an estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m2, and normal serum calcium and lactate dehydrogenase (LDH) levels. His bone marrow contained 58% plasma cells, which showed the 17p deletion abnormality (Fig 1). He was treated with vertebroplasty and alternating chemotherapy with carmustine, vincristine, cyclophosphamide, melphalan, and prednisone and vincristine, carmustine, doxorubicin and dexamethasone. Because of progressive disease, salvage therapy with bortezomib and dexamethasone was administered with no response. The patient was then switched to lenalidomide and dexamethasone, which yielded minimal response. He underwent autologous stem-cell transplantation (ASCT) with melphalan 200 mg/m2 as high-dose therapy in February 2011, which led to a partial response, but in December 2011, progressive disease was documented, and the patient was enrolled in a clinical trial of carfilzomib monotherapy, with stable disease for 33 cycles. In October 2014 serum M protein rose to 38.6 g/L, with 24-hour kappa light-chain urine protein excretion of 840 mg, serum creatinine of 2.1 mg/dL, and an eGFR of 41 mL/min/1.73 m2. He presented to discuss ongoing treatment options.

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