-
Kidney International Jan 2020Immune checkpoint inhibitors have dramatically improved cancer therapy for many patients. These humanized monoclonal antibodies against various immune checkpoints... (Review)
Review
Immune checkpoint inhibitors have dramatically improved cancer therapy for many patients. These humanized monoclonal antibodies against various immune checkpoints (receptors and ligands) effectively treat a number of malignancies by unleashing the immune system to destroy cancer cells. These drugs are not excreted by the kidneys or liver, have a long half-life, and undergo receptor-mediated clearance. Although these agents have greatly improved the prognosis of many cancers, immune-related end organ injury is a complication that has come to light in clinical practice. Although less common than other organ involvement, kidney lesions resulting in acute kidney injury and/or proteinuria are being described. Acute tubulointerstitial nephritis is the most common lesion seen on kidney biopsy, while acute tubular injury and glomerular lesions occur less commonly. Clinical findings and laboratory tests are suboptimal in predicting the underlying renal lesion, making kidney biopsy necessary in the majority of cases to definitely diagnose the lesion and potentially guide therapy. Immune checkpoint inhibitor discontinuation and corticosteroid therapy are recommended for acute tubulointerstitial nephritis. Based on a handful of cases, re-exposure to these drugs in patients who previously developed acute tubulointerstitial nephritis has been mixed. Although it is unclear whether re-exposure is appropriate, it should perhaps be considered in patients with limited options. When this approach is taken, patients should be closely monitored for recurrence of acute kidney injury. Treatment of cancer in patients with a kidney transplant with immune checkpoint inhibitors risks the development of acute rejection in some patients and requires close surveillance.
Topics: Acute Kidney Injury; Antineoplastic Agents, Immunological; Graft Rejection; Humans; Immune Checkpoint Inhibitors; Kidney Glomerulus; Kidney Transplantation; Neoplasms; Proteinuria
PubMed: 31685311
DOI: 10.1016/j.kint.2019.07.022 -
Scientific Reports Nov 2023We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional,... (Clinical Trial)
Clinical Trial
We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.
Topics: Humans; Budesonide; Glomerulonephritis, IGA; Prospective Studies; Glomerular Filtration Rate; Proteinuria
PubMed: 37978255
DOI: 10.1038/s41598-023-47393-1 -
Transplantation Proceedings Mar 2022Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in...
BACKGROUND
Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake.
METHODS
We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records.
RESULTS
A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m (IQR, 25 mL/min/1.73 m). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis.
CONCLUSIONS
The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.
Topics: Acidosis; Adolescent; Cross-Sectional Studies; Eating; Female; Hospitals, Teaching; Humans; Kidney Transplantation; Male; Prevalence; Proteinuria; Transplant Recipients
PubMed: 35125235
DOI: 10.1016/j.transproceed.2021.12.019 -
Journal of Feline Medicine and Surgery Jun 2023The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats.
OBJECTIVES
The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats.
METHODS
A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a -test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test.
RESULTS
Relative to the control group, cats in the CS group had significantly lower serum creatinine ( <0.001) and albumin concentrations ( <0.001), urine specific gravity ( = 0.024) and hematocrit ( = 0.003), and higher serum phosphorus ( <0.001), potassium ( <0.001) and globulin concentrations ( <0.001), white blood cell count ( <0.001) and urine protein:creatinine ratio ( = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups.
CONCLUSIONS AND RELEVANCE
The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.
Topics: Cats; Animals; Azotemia; Creatinine; Retrospective Studies; Case-Control Studies; Cross-Sectional Studies; Kidney; Proteinuria; Acute Kidney Injury; Biomarkers; Urea; Cat Diseases
PubMed: 37350300
DOI: 10.1177/1098612X231179883 -
Jornal Brasileiro de Nefrologia 2023
Topics: Humans; Aged; Proteinuria
PubMed: 37185894
DOI: 10.1590/2175-8239-JBN-2023-E006en -
International Journal of Molecular... May 2022We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing...
We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment.
Topics: Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Kidney Diseases; Podocytes; Proteinuria; Rats
PubMed: 35682697
DOI: 10.3390/ijms23116018 -
Ginekologia Polska 2022Proteinuria is one of the diagnostic criteria of preeclampsia (PE). Measurement of 24-hour urine protein is the gold standard method for detection of proteinuria in PE....
OBJECTIVES
Proteinuria is one of the diagnostic criteria of preeclampsia (PE). Measurement of 24-hour urine protein is the gold standard method for detection of proteinuria in PE. The 24-hour urine sampling is time-consuming, and inconvenient. To evaluate the accuracy of protein/creatinine (P/C) ratio in detection of significant proteinuria (> 1 g/24-hours urine) in PE.
MATERIAL AND METHODS
One hundred and ten (110) preeclamptic women were included in this study and admitted for blood pressure monitoring, 24-hour urine collection, fetal well-being assessment and spot urine sample for measuring of P/C ratio. After thorough history and clinical examination, routine antenatal investigations were done for the women included in the study according to the hospital`s protocol, and to exclude pre-existing chronic renal disease. Twenty-four-hour urine collection started on the morning following hospital admission. Spot urine samples were obtained shortly before the 24-hour urine collection for measuring of P/C ratio. Collected data statistically analyzed to evaluate the accuracy of P/C ratio in detection of significant proteinuria in PE.
RESULTS
The P/C ratio of 1.35 ± 2.54 had 94.4% sensitivity, 94.9% specificity, 97.1% positive predictive value (PPV), 90.2% negative predictive value (NPV), and 94.5% overall accuracy in detection of significant proteinuria (> 1 g/24-hour urine) in PE.
CONCLUSIONS
The P/C ratio of 1.35 ± 2.54 had 94.4% sensitivity, 94.9% specificity, 97.1% PPV, 90.2% NPV, and 94.5% overall accuracy in detection of significant proteinuria (> 1 g/24-hour urine) in PE. This study suggests the use of P/C ratio as an alternative to 24-hour urine protein to detect significant proteinuria in PE.
Topics: Female; Humans; Pregnancy; Pre-Eclampsia; Creatinine; Prospective Studies; Urinalysis; Proteinuria; Sensitivity and Specificity
PubMed: 35156696
DOI: 10.5603/GP.a2021.0233 -
BMC Nephrology Jan 2020Hypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of...
BACKGROUND
Hypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism.
METHODS
We assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels..
RESULTS
One thousand six hundred ten patients (64 ± 15 years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30-45 and 15-30 ml/min/1.73m in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT, p = 0.032). Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was - 0.05(- 0.26, 0.23) ml/min/1.73m, reaching 1.7(1.3, 2.4) ml/min/1.73m by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT.
CONCLUSIONS
We confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.
Topics: Aged; Aged, 80 and over; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypothyroidism; Male; Middle Aged; Proteinuria; Renal Insufficiency, Chronic; Thyroxine
PubMed: 32000713
DOI: 10.1186/s12882-019-1677-3 -
BMC Nephrology May 2022Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the...
BACKGROUND
Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown.
METHODS
Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline.
RESULTS
At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea.
CONCLUSION
KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.
Topics: Drugs, Chinese Herbal; Female; Glomerulonephritis, IGA; Humans; Male; Proteinuria; Retrospective Studies; Treatment Outcome; Tripterygium
PubMed: 35538439
DOI: 10.1186/s12882-022-02814-7 -
Frontiers in Public Health 2022Frailty is a commonly occurring geriatric condition that increases the risk of adverse health outcomes. The factors and predictors behind frailty are not yet well... (Observational Study)
Observational Study
Frailty is a commonly occurring geriatric condition that increases the risk of adverse health outcomes. The factors and predictors behind frailty are not yet well understood. A better understanding of these factors can enable prevention of frailty in elderly patients. The objective of this study was to determine the association between proteinuria and frailty in US individuals with metabolic syndrome (MetS). Data from the National Health and Nutrition Examination Survey III (NHANES III, 1988-1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. This is a cross-sectional study, and proteinuria and frailty were measured only once at enrollment. The study included 2,272 participants with MetS aged 40-90 years from the NHANES III. The participants underwent assessments to evaluate frailty and frailty components (low body weight, weakness, exhaustion, low physical activity, and slow walking). Proteinuria was represented as albumin-to-creatinine ratio (ACR) (mg/g) and divided into tertiles: T1-normal range (ACR <30 mg/g), T2-microalbuminuria (ACR 30-299 mg/g), and T3-macroalbuminuria (ACR ≥ 300 mg/g). We applied multiple logistic regression to determine the odds ratios (ORs) of frailty for T2 vs. T1 and T3 vs. T1 in both sexes. In the adjusted analysis for male participants, the ORs of frailty for T2 and T3 vs. T1 were 3.106 (95% confidence interval [CI] = 1.078-8.948, = 0.036) and 14.428 (95% CI = 4.231-49.193, < 0.001), respectively. For female participants, the ORs of frailty for T2 and T3 vs. T1 were 1.811 (95% CI = 1.071-3.063, = 0.027) and 2.926 (95% CI = 1.202-7.124, = 0.018), respectively. The positive association between T2 and T3 vs. T1, and frailty were statistically significant. The trends of higher likelihood of every frailty component were also statistically significant across increasing tertiles of proteinuria after multiple levels of adjustment for covariates ( < 0.05). Increased proteinuria levels were positively associated with frailty and each frailty component. Proteinuria might be a useful maker for frailty in individuals with MetS.
Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Frail Elderly; Frailty; Humans; Male; Metabolic Syndrome; Middle Aged; Nutrition Surveys; Proteinuria
PubMed: 35359757
DOI: 10.3389/fpubh.2022.847533