Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.

Introduction: Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway. No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by complement biomarkers) of iptacopan were assessed in patients with C3G. Methods: In this phase 2, multicenter, open-label, single-arm, nonrandomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent kidney transplant [KT] cohort) received iptacopan twice daily (bid) for 84 days (days 1-21: 10-100 mg; days 22-84: 200 mg). The primary end point was the urine protein-to-creatinine ratio (UPCR; native cohort) and the change in the C3 deposit score of kidney biopsy (recurrent KT cohort). The complement pathway measures included Wieslab assay, soluble C5b9, and serum C3 levels. Results: A total of 27 patients (16 native cohort and 11 recurrent KT cohort) were enrolled and all completed the study. In the native cohort, UPCR levels decreased by 45% from baseline to week 12 (P = 0.0003). In the recurrent KT cohort, the median C3 deposit score decreased by 2.50 (scale: 0-12) on day 84 versus baseline (P = 0.03). Serum C3 levels were normalized in most patients; complement hyperactivity observed pretreatment was reduced. Severe adverse events (AEs) included post-biopsy hematuria and hyperkalemia. No deaths occurred during the study. Conclusion: Iptacopan resulted in statistically significant and clinically important reductions in UPCR and normalization of serum C3 levels in the native cohort and reduced C3 deposit scores in the recurrent KT cohort with favorable safety and tolerability. (ClinicalTrials.gov identifier: NCT03832114).

Review of the Role of Rituximab in the Management of Adult Minimal Change Disease and Immune-Mediated Focal and Segmental Glomerulosclerosis.

Background: Minimal change disease and primary FSGS are podocytopathies but are also immune-mediated diseases. Rituximab acts via multiple mechanisms by tilting the balance between autoreactive B and T cells in favor of regulatory B and T cells. The consequences are decreased production of cytokines, chemokines, and permeability factors by these cells. In the past decade, we have seen the discovery of autoantibodies mediating nephrotic syndrome (anti-annexin A2 antibody, anti-UCHL1 antibody, and anti-nephrin antibody), and rituximab decreases their production. Rituximab also binds to podocyte SMPDL3b and has direct podocyte actions. Summary: Rituximab's role in managing these primary podocytopathies has been discussed in this brief review. Rituximab has been used extensively in children and adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, rituximab is not very promising in adult steroid-resistant nephrotic syndrome. Although ofatumumab would cause prolonged B-cell depletion and is fully humanized, it is unclear if it is superior to rituximab in preventing relapse of nephrotic syndrome. Key Messages: Rituximab therapy can induce prolonged remission in adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, no good data exist on using rituximab in steroid-resistant nephrotic syndrome.

A comparison of the utility of the urine dipstick and urine protein-to-creatinine ratio for predicting microalbuminuria in patients with non-diabetic lifestyle-related diseases -a comparison with diabetes.

BACKGROUND: The utility of dipstick proteinuria for predicting microalbuminuria in non-diabetic lifestyle-related diseases compared with the urine protein-to-creatinine ratio (uPCR) and the effect of dipstick proteinuria on the cut-off value (CO) and accuracy of uPCR are unclear. METHODS: The subjects included Japanese patients ≥ 18 years old with lifestyle-related diseases who had an estimated glomerular filtration rate of ≥ 15 ml/min/1.73 m2 and uPCR of < 0.5 g/gCr at initiation. Urine dipstick, uPCR and urine albumin-to-creatinine ratio (uACR) were measured three times per case. Microalbuminuria was defined as uACR of 30-299 mg/gCr for at least 2 of 3 measurements. Youden's Index was used as the optimal CO. Factors associated with microalbuminuria were analyzed using a logistic regression model. RESULTS: In 313 non-diabetic cases (median 70.8 years old), 3 dipstick proteinuria measurements were independently useful for detecting microalbuminuria, and the CO was set when a trace finding was obtained at least 1 of 3 times (sensitivity 0.56, specificity 0.80, positive predictive value [PPV] 0.73, negative predictive value [NPV] 0.65). A single uPCR measurement was more useful than 3 dipstick measurements, and was useful for detecting microalbuminuria even in cases with three consecutive negative proteinuria findings, indicating that the CO of the second uPCR with G1-3a (n = 136) was 0.06 g/gCr (sensitivity 0.76, specificity 0.84. PPV 0.68, NPV 0.89), while that with G3-b4 (n = 59) was 0.10 g/gCr (sensitivity 0.56, specificity 0.91. PPV 0.83, NPV 0.71). The sum of 3 uPCRs was useful for detecting microalbuminuria in cases with G1-3a (sensitivity 0.67, specificity 0.94, PPV 0.82, NPV 0.86) and G3b-4 (sensitivity 0.78, specificity 0.94, PPV 0.91 NPV 0.83), with both COs being 0.23 g/gCr. These COs of microalbuminuria did not change when trace or more proteinuria was included, although the sensitivity increased. A high uPCR and low urine specific gravity or creatinine level were independent factors for uACR ≥ 30 mg/gCr in cases with negative proteinuria, although the uPCR was a major predictive factor of a uACR ≥ 30 mg/gCr. CONCLUSIONS: The uPCR (preferably determined using early-morning urine), including in dipstick-negative proteinuria cases with non-diabetic lifestyle-related diseases, can aid in the early detection of microalbuminuria. TRIAL REGISTRATION: Retrospectively registered.

Clinical relevance of postoperative proteinuria for prediction of early renal outcomes after kidney transplantation.

BACKGROUND: Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. METHODS: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2-3 weeks postoperatively), and 3-6 months postoperatively. RESULTS: The median age of the patients was 51 years (interquartile range, 43-59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. CONCLUSION: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

Comparisons of urine protein-to-creatinine ratios and their dynamic change patterns during labor at term between normal pregnant women and women with pregnancy induced hypertension.

Introduction: To evaluate patterns of change in the urine protein-to-creatinine ratios (uPCRs) during labor at term between normal and women with pregnancy-induced hypertension (PIH). Methods: This is an observational study in tertiary referral hospital, recruiting 269 women at term delivery in Taiwan from April 19, 2019 to April 18, 2021. uPCRs in four phases (latent, active, recovery and early postpartum) and related clinical data at delivery were collected. Multivariate analyses with a linear regression model were performed to analyze continuous variables after adjusting for clinical data between two groups. Results: Based on exclusion criteria, 68 normal and 24 pregnant women with PIH were included. There were no differences in the uPCR or the proportion cases of uPCRs ≥ 300 mg/g between normal and PIH group in the four phases. There was a statistically significant tendency for the proportion of uPCRs ≥ 300 mg/g to increase from the latent to the early postpartum phase in both groups. The proportion of uPCRs ≥ 300 mg/g significantly increased from the active to the recovery phase and then declined from the recovery to the early postpartum phase in the normal group. Thus no differences in uPCRs cases change between any two phases in women with PIH, except the duration above stated. Conclusion: This is the first study to demonstrate that uPCRs data are not different between normal pregnant and PIH groups during the course of labor, but it did show different dynamic change patterns throughout the labor phases.

Evaluation of Heller's reaction and the urine dipstick method alone or in combination to detect proteinuria in sheep.

BACKGROUND: Urine dipstick and Heller's reaction are easy first-line screening tests for the detection of proteinuria; however, the performance of these methods in alkaline ovine urine is largely unknown. OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of Heller's reaction alone or in combination with dipstick for the detection of proteinuria in sheep, using the urine protein to creatinine ratio (UP/C) with two cut-off values as the reference method. METHODS: Ninety-eight urine samples were collected from sheep using the transient apnea method. Heller's reaction, the dipstick method, and the UP/C ratio were used to assess proteinuria. The results were statistically analyzed twice, based on two different UP/C cut-off values of 0.2 and 0.5. Cohen's kappa value was used to determine the agreement between the UP/C ratios and Heller's reaction, the dipstick method, or the combination of methods. Sensitivity, specificity, and positive and negative likelihood ratios were calculated. ROC curves were also generated, and the areas under the curve (AUC) were evaluated to determine the optimal threshold for the numerical values of the two methods. RESULTS: Heller's reaction is more specific (96.67% and 96.00% when the cut-off value is 0.2 and 0.5, respectively) than the dipstick method, while the dipstick method was more sensitive (91.18% and 91.30%, when the cut-off value was 0.2 and 0.5, respectively) than Heller's reaction for the detection of proteinuria. Both tests were accurate when any grade >0 was considered positive. CONCLUSIONS: Proteinuria can almost be excluded in ovine urine samples with negative Heller's reaction and dipstick test.

The development of end stage renal disease in two patients with PMM2-CDG.

We report two patients with PMM2-CDG who developed end stage renal disease (ESRD). Renal abnormalities of clinical significance have only been reported in about 6% of patients with PMM2-CDG and have rarely been reported as the cause of death. Given the recurrent episodes of acute kidney injury associated with hospital admissions and the accelerated development of ESRD thereafter in our two patients, we recommend proactively involving Nephrology early in the care of these patients.

Clinical, pathological, and genetic characteristics of cases with asymptomatic proteinuria not manifesting nephrotic syndrome at onset: a single-center retrospective study.

BACKGROUND: Cases with asymptomatic proteinuria (ASP) not manifesting nephrotic syndrome often pathologically show focal segmental glomerulosclerosis (FSGS). However, characteristics of those cases had not been intensively studied so far. METHODS: We retrospectively reviewed clinical, pathological, and genetic characteristics of 37 children (median age, 9.3 years) who underwent renal biopsy for persistent isolated proteinuria (urine protein-to-creatinine ratio: UP/C, > 0.2 g/g) between 2003 and 2019. Targeted next-generation sequencing (NGS) was utilized for all patients with FSGS, excluding those with secondary FSGS. RESULTS: At biopsy, all patients with FSGS (N = 14) had UP/C ≥ 0.5 g/g and the median UP/C was significantly higher in those with FSGS than those with minor glomerular abnormalities (MGA) (N = 23) (1.49 vs. 0.53 g/g, P < 0.001). Causative variants were found in seven patients with FSGS (TRPC6, WT1, ACTN4, and INF2 in 3, 2, 1, and 1 patient, respectively): all gene variants were in genes manifesting autosomal dominant inheritance mode. The proportion of the perihilar variant was significantly higher in the genetic FSGS patients than in the non-genetic FSGS patients (4/7 vs. 0/7, P < 0.05). Kaplan-Meier analysis showed that the renal survival rate after ASP diagnosis was significantly lower in the genetic FSGS patients than in the non-genetic FSGS and the MGA patients (P < 0.001). CONCLUSIONS: UP/C was a simple and useful predictive parameter for the diagnosis of FSGS. APS without nephrotic syndrome at onset may be associated with autosomal dominant causes of FSGS, especially in those with the perihilar variant.

Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance.

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria. Although the reference standard for measuring urinary protein excretion is a 24-hour urine collection, spot urine protein-to-creatinine ratio is a reasonable "rule-out" test for proteinuria. Urine dipstick screening for proteinuria does not provide any clinical benefit and should not be used to diagnose proteinuria. The classic cutoff cited to define proteinuria during pregnancy is a value of >300 mg/24 hours or a urine protein-to-creatinine ratio of at least 0.3. Using this cutoff, the rate of isolated proteinuria in pregnancy may reach 8%, whereas preeclampsia occurs among 3% to 8% of pregnancies. Although this threshold is widely accepted, its origin is not based on evidence on adverse pregnancy outcomes but rather on expert opinion and results of small studies. After reviewing the available data, the most important factor that influences maternal and neonatal outcome is the severity of blood pressures and presence of end organ damage, rather than the excess protein excretion. Because the management of gestational hypertension and preeclampsia without severe features is almost identical in frequency of surveillance and timing of delivery, the separation into 2 disorders is unnecessary. If the management of women with gestational hypertension with a positive assessment of proteinuria will not change, we believe that urine assessment for proteinuria is unnecessary in women who develop new-onset blood pressure at or after 20 weeks' gestation. Furthermore, we do not recommend repeated measurement of proteinuria for women with preeclampsia, the amount of proteinuria does not seem to be related to poor maternal and neonatal outcomes, and monitoring proteinuria may lead to unindicated preterm deliveries and related neonatal complications. Our current diagnosis of preeclampsia in women with chronic kidney disease may be based on a change in protein excretion, a baseline protein excretion evaluation is critical in certain conditions such as chronic hypertension, diabetes, and autoimmune or other renal disorders. The current definition of superimposed preeclampsia possesses a diagnostic dilemma, and it is unclear whether a change in the baseline proteinuria reflects another systemic disease such as preeclampsia or whether women with chronic disease such as chronic hypertension or diabetes will experience a different "normal" pattern of protein excretion during pregnancy. Finally, limited data are available regarding angiogenic and other biomarkers in women with chronic kidney disease as a potential aid in distinguishing the worsening of baseline chronic kidney disease and chronic hypertension from superimposed preeclampsia.

Is proteinuria a rare condition in apparently healthy and sick cats? A feline practice experience (2007-2018).

Background: Proteinuria is assumed to be less frequent in cats than in dogs and is mainly associated with chronic kidney disease (CKD). Aim: The current study aimed to evaluate and compare urine protein-to-creatinine (UPC) values retrospectively in cats visited for comprehensive annual health check or for presenting systemic clinical signs related to CKD. Methods: UPC ratio was retrospectively evaluated in 112 owned cats, out of which 51 (45.5%) were apparently healthy cats according to their owners who visited for comprehensive annual health checks and 61 (54.5%) sick cats, presenting systemic clinical signs suggesting CKD, such as weight loss or polyuria/polydipsia, among others. Results: Based on UPC, the present study found that 54.5% of all cats included were borderline proteinuric or proteinuric, having increased UPC (UPC ≥ 0.2), with 35.7% included in the sick group and 18.7% in the health-check group. Increased UPC was also statistically associated with azotemia and isosthenuria (urinary-specific gravity between 1,008 and 1,035) in both sick and health-check groups of cats. Conclusion: Independent of the reason for their medical visit, it could be concluded that borderline proteinuria and proteinuria were statistically mainly related to CKD in cats. Furthermore, the measurement of UPC could be very useful in the detection and management of CKD in apparently healthy cats during a medical visit for annual health check irrespective of the age.

Effect of telmisartan, angiotensin-converting enzyme inhibition, or both, on proteinuria and blood pressure in dogs.

BACKGROUND: The use of telmisartan (TEL), an angiotensin-receptor blocker, for the control of systemic hypertension and proteinuria in dogs has not been reported extensively in a clinical setting. OBJECTIVES: To determine the effects of an angiotensin-converting enzyme inhibitor (ACEi) alone, ACEi in combination with TEL, or TEL alone on systolic blood pressure and proteinuria in dogs with protein losing nephropathy (PLN). ANIMALS: Forty-two client-owned dogs being treated for PLN. METHODS: Retrospective observational study of medical records of dogs at a university teaching hospital from 2012 to 2018 with the use of benazepril or enalapril alone, TEL alone, or both modalities for the management of PLN. Noninvasive blood pressure and urine protein to creatinine ratio (UPC) were compared among the treatment groups over time. A multivariable mixed-effects linear regression model followed by post hoc analysis was used to estimate the marginal means and differences between the treatment groups. RESULTS: In comparison to group ACEi alone, combination treatment of an ACEi with TEL significantly reduced (P = .007) systolic blood pressure by 13 mm Hg (95% confidence interval [95% CI]: 4-22 mm Hg). Angiotensin-converting enzyme inhibitor + TEL in comparison to ACEi alone showed significant (P = .01) reduction in UPC of 2.5 (95% CI: 0.6-4.4). The UPC of group ACEi + TEL was significantly lower (P = .01) in comparison to TEL alone by 3.8 (95% CI: 0.8-6.8). CONCLUSIONS AND CLINICAL IMPORTANCE: Telmisartan can be used to treat systemic hypertension and proteinuria in dogs.

Effects of telmisartan on proteinuria and systolic blood pressure in dogs with chronic kidney disease.

Renal proteinuria is associated with promoted renal dysfunction and a shorter survival period in dogs with chronic kidney disease (CKD). Renin angiotensin- aldosterone system inhibitors are primarily used to treat renal proteinuria. In this retrospective, open-label study, we aimed to evaluate the anti-proteinuric and anti-hypertensive effects of telmisartan (angiotensin II receptor blocker) in dogs with proteinuric CKD. A total of 28 dogs with proteinuric CKD were included in the study, all dogs received telmisartan 1 mg/kg q24h, PO. The urine protein-to-creatinine ratio (UPC), urine albumin-to-creatinine ratio (UAC) and systolic blood pressure (SBP) decreased significantly after telmisartan administration (P < 0.05). The median rate of change in UPC, UAC and SBP at Day 120 were - 65.1%, -75.9% and - 9.7%. Ten dogs (36.7%) achieved UPC < 1.0 at Day 120, of which six dogs had UPC < 0.5. A reduction of UPC to ≥50% was achieved in 10 dogs (36%) at Day 45 and 17 dogs (61%) at Day 120. Seventeen dogs (61%) had hypertension at baseline, of which 10 dogs (59%) had SBP < 160 mmHg at Day 120. Two-way repeated measures analysis of variance did not attribute the observed changes in SBP, UPC or UAC to feeding with a renal diet. In conclusion, telmisartan therapy provides anti-proteinuric and anti-hypertensive effects in dogs with proteinuric CKD.

Comparisons of Dipstick Test, Urine Protein-to-Creatine Ratio, and Total Protein Measurement for the Diagnosis of Preeclampsia.

Preeclampsia affects 2-5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality. We aimed to extensively evaluate proteinuria in women with preeclampsia and to determine the analytical sensitivity and specificity of and the cutoff values for urine protein-to-creatinine ratio (UPCR) and total protein in 24 h urine samples. This study included 88 women. We used the urine dipstick test, UPCR, and total protein measurement in a 24 h urine sample. The patients were divided in gestational hypertension (GH, n = 44) and preeclampsia (PE, n = 44) groups. In the GH group, 25% (11/44) of the patients presented incidentally positive results. UPCR and total protein in 24 h urine specimens were increased in the GH group compared to the PE group. Receiver operating characteristic analysis showed a UPCR cutoff of 30 mg/mmol as significant for preeclampsia, while the sensitivity and specificity were 89% (95% CI, 75-97) and 100% (95% CI, 87-100), respectively. In the 24 h urine protein test, sensitivity and specificity were 80% (95% CI, 61-92) and 100% (95% CI, 88-100), respectively, for the cutoff value of 0.26 g/24 h. In comparison to the other commonly used tests here considered, UPCR determination is a reliable, relatively faster, and equally accurate method for the quantitation of proteinuria, correlates well with 24 h urine protein estimations, and could be used as an alternative to the 24 h proteinuria test for the diagnosis of preeclampsia.

Changes in Renal Function After Switching From TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study.

BACKGROUND: Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals but the impact on estimated glomerular filtration rate (eGFR) remains unclear. METHODS: In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, we estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models. RESULTS: Of 3520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (-1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5-2.5) if the baseline eGFR was 60-89 mL/min, and 4.1 mL/min (95% CI, 1.6-6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3-9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR. CONCLUSIONS: Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction.

Renoprotective Effects of Additional SGLT2 inhibitor Therapy in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3b-4: A Real World Report From A Japanese Specialized Diabetes Care Center.

BACKGROUND: Large randomized clinical trials of patients with type 2 diabetes mellitus (T2DM) and at high risk for cardiovascular disease revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced renal events. However, the trials included small numbers of patients with moderate-to-severe chronic kidney disease (CKD). Therefore, the renoprotective effects of SGLT2 inhibitors remain unknown in T2DM patients complicated with impaired renal function. We examined if SGLT2 inhibitors conferred beneficial effects on kidney function in T2DM patients with CKD. METHODS: We retrospectively recruited T2DM patients who were newly treated with add-on of SGLT2 inhibitors and suffered from moderate-to-severe renal impairment with CKD stages 3b-4 (15 < estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2), at initiation of SGLT2 inhibitor therapy. We analyzed T2DM patients with moderate-to-severe renal impairment who continued to use SGLT2 inhibitors for at least 1 year. We investigated the effects of SGLT2 inhibitor therapy on 1-year changes in eGFR and urinary protein excretion before and after the treatment. RESULTS: We analyzed 42 T2DM patients with median eGFR of 40.4 mL/min/1.73 m2. One-year SGLT2 inhibitor therapy lowered median hemoglobin A1c (HbA1c) levels from 7.6% to 7.5% (not significant). Body weight and blood pressure were significantly decreased, and hemoglobin was significantly increased. The median value of eGFR after 1 year of SGLT2 inhibitor therapy was 41.0 mL/min/1.73 m2, with no significant difference compared with baseline. The annual decline in eGFR improved significantly after SGLT2 inhibitor therapy (eGFR: (median), pre: -3.8, vs. post: 0.1 mL/min/1.73 m2 per year, P < 0.01). We also found a significant decrease in urinary protein excretion after SGLT2 inhibitor therapy (urinary protein-to-creatinine ratio: (median), pre: 0.36, vs. post: 0.23 g/g creatinine, n = 35, P < 0.01). CONCLUSIONS: This study revealed the promising observations that add-on treatment with SGLT2 inhibitors exerted significant renoprotective effects, culminating in improvements in annual decline in eGFR and urinary protein excretion in T2DM patients with CKD stages 3b-4, but did not significantly reduce HbA1c. Further prospective clinical trials are warranted to fully elucidate the effects of SGLT2 inhibitors on glycemic control and renal function in T2DM patients with moderate-to-severe renal impairment.

Early-stage predictors for treatment responses in patients with active lupus nephritis.

OBJECTIVE: We analyzed data of lupus nephritis (LN) patients to find parameters that can predict remission. METHODS: Sixty-four LN patients who were diagnosed with class III, IV, V or V + III/IV by renal biopsy and were followed up for more than six months in our center were enrolled retrospectively. Receiver operating characteristic curves were used to test the predictive values of urinary protein-to-creatinine ratio (UPCR), serum albumin and complement C3 at the first, second and third months as predictors for remission at the sixth month. RESULTS: The patients' renal pathologies were class III (five cases), class IV (33 cases), class V (nine cases) and class V + III/IV (17 cases). All patients received standard immunosuppressive therapy. Forty-six (71.9%) patients (grouped as the remission group) achieved remission at the end of the sixth month, including 23 complete remissions and 23 partial remissions. The other 18 patients were grouped as the no-remission group. There were no significant differences in clinical data, proportion of immunosuppressive therapy or renal pathological characteristics between the remission group and no-remission group at baseline, except the serum urea nitrogen of the remission group was lower than in the no-remission group. The UPCR were significantly lower in the remission group than in the no-remission group at months 1, 2, 3 and 6, respectively, while the serum albumin was significantly higher in the remission group than in the no-remission group at months 3 and 6, respectively. There were no significant differences in serum creatinine between the remission group and no-remission group, except at month 1. The C3 levels were higher in the remission group than in the no-remission group at months 1, 2 and 3, respectively. The areas under the curve (AUC) of the change percentage of UPCR at month 3 and the serum albumin at month 3 were the most significant (AUC 0.778, p = 0.002; AUC 0.773, p = 0.001, respectively). The cutoff value of the change percentage of UPCR at month 3 was 59%. The cutoff value of serum albumin at month 3 was 32.9g/l. CONCLUSION: The change percentage of UPCR ≥59% and the serum albumin ≥32.9 g/l at the third month were valuable for predicting remission at the sixth month in LN. Because of the small-size and retrospective nature, this study needs to be validated.

An unresolved issue: The relationship between spot urine protein-to-creatinine ratio and 24-hour proteinuria.

OBJECTIVE: To investigate the relationship between spot urine protein-to-creatinine (sP/Cr) ratio and 24-h protein excretion in patients with different diagnoses. METHODS: This retrospective study analysed data from the medical records of patients admitted for24-h proteinuria determination who also had sP/Cr ratio data for the same day. RESULTS: A total of 1222 urine samples obtained from 694 adult outpatients were analysed. The mean ± SD age of the patients was 53.6 ± 15.9 years. The mean ± SD 24-h proteinuria and sP/Cr were 1.7 ± 2.4 g/day and 1.8 ± 2.4, respectively. The correlation between the sP/Cr and 24-h protein excretion was high (R2 = 0.89). The sP/Cr ratio accounted for 72% of the variability in 24-h proteinuria in the entire study population. Areas under the curve for 24-h proteinuria at 0.3 g/day, 1.0 g/day and 3.0 g/day were 0.940, 0.966, and 0.949, respectively. The mean + 2SD limits of agreement were between +2.99 and -2.73 g/day according to the Bland Altman analysis. CONCLUSION: This current study found a clinically unacceptable deviation between 24-h proteinuria and sP/Cr ratio. Therefore, the sP/Cr ratio cannot replace 24-h proteinuria. A new method using spot urine protein and creatinine values that is able to minimize under or over estimation is still warranted.

Does blood contamination of urine compromise interpretation of the urine protein to creatinine ratio in dogs?

AIMS: To determine the effect of contamination of urine with 0-5% blood, varying in haematocrit and protein concentrations, on the urine protein to creatinine ratio (UPC) in dogs, and to determine whether the colour of urine can be used to aid interpretation of UPC results. METHODS: Urine samples were collected by free catch from 18 dogs, all of which had UPC <0.2. Venous blood samples were also collected from each dog, and the blood from each dog was added to its own urine to produce serial concentrations of 0.125-5% blood. The colour of each urine sample was recorded by two observers scoring them as either yellow, peach, orange, orange/red or red. Protein and creatinine concentrations were determined, and dipstick analysis and sediment examination was carried out on each sample. Based on colour and dipstick analysis, samples were categorised as either having microscopic, macroscopic or gross haematuria. A linear mixed model was used to examine the effect of blood contamination on UPC. RESULTS: The uncontaminated urine of all 18 dogs had a UPC <0.2. Adding blood to the urine samples resulted in an increase in UPC at all contamination concentrations compared to the non-contaminated urine (p<0.001). None of the 54 samples with microscopic haematuria had UPC >0.5. For 108 samples with macroscopic haematuria the UPC was >0.5 in 21 samples (19.4 (95% CI=13.1-27.9)%), and for 54 samples with gross haematuria 39 (72 (CI=59.1-82.4)%) had a UPC >0.5. No samples had a UPC >2.0 unless the blood contamination was 5% and only 3/18 (17%) samples at this blood contamination concentration had a UPC >2.0. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that while blood contamination of ≥0.125% does increase the UPC, if the urine remains yellow (microscopic haematuria), then there is negligible chance that a UPC >0.5 will be solely due to the added blood. In that scenario, attributing the proteinuria present to the haematuria in the sample would be inappropriate. However blood contamination that results in discolouration of the urine sample from yellow (indicating macroscopic or gross haematuria) could increase the UPC above the abnormal range and would need to be considered as a differential for the proteinuria. Thus knowledge of urine colour, even if limited to simple colour scores (yellow, discoloured, red) could be utilised to aid interpretation of the UPC in samples with haematuria.

Analysis of Proteinuria Estimation Methods in Hypertensive Disorders of Pregnancy.

PURPOSE OF THE STUDY: The gold-standard 24-h urine collection method for protein estimation is inconvenient and is associated with a delay in laboratory analysis. This study was undertaken to compare sulphosalicylic acid test, urine dipstick test, urine protein-to-creatinine ratio with 24-h urine protein estimation in pre-eclampsia cases. METHODS: This is a comparative study and consists of a single group of 764 subjects. This study was conducted in the Department of Obstetrics and Gynaecology in collaboration with the Department of Biochemistry, JIPMER, Pondicherry, India, from February 2011 to January 2014. The subjects included were 764 pre-eclampsia women. A first voided morning sample was obtained for sulphosalicylic acid test, dipstick test, urine protein and creatinine estimation and urine culture, and subsequent urine samples were collected for the 24-h urine protein estimation. MAIN FINDINGS: For significant proteinuria, sulphosalicylic acid test with 1 + proteinuria has sensitivity, specificity, PPV and NPV of 59, 48, 39, 67, whereas with 2 + has sensitivity, specificity,PPV and NPV of 44, 88, 75 and 67%, respectively, dipstick test with 1 + proteinuria has sensitivity, specificity, PPV and NPV of 71, 52, 54 and 70%, whereas with 2 + has sensitivity, specificity,PPV and NPV of 49, 87, 75 and 69%, respectively. The spot urine protein-to-creatinine ratio and 24-h urine protein were significantly correlated (r = 0.98; p < 0.0001). The cut-off value for the protein-to-creatinine ratio as an indicator of protein excretion ≥ 300 mg/day was 0.285. The sensitivity, specificity PPV and NPV were 100, 99, 100 and 99%, respectively. CONCLUSION: The spot urine protein-to-creatinine ratio is a better method for estimation of proteinuria in pre-eclampsia.

Clinical Consequences of Hypertriglyceridemia-Associated Proteinuria in Miniature Schnauzers.

BACKGROUND: Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia-associated proteinuria (HTGP) is unknown. OBJECTIVE: To investigate prevalence of hypertension, decreased antithrombin III activity, and cardiac disease in Miniature Schnauzers with and without HTGP. ANIMALS: Thirty-two Miniature Schnauzers ≥7 years old. METHODS: Prospective case-control study. Data collected from dogs included a CBC, biochemistry panel, urinalysis, urine protein-to-creatinine ratio, urine cortisol-to-creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombin III activity, and serum cardiac troponin I concentration. Results from dogs with HTGP (serum triglyceride concentration ≥ 100 mg/dL and urine protein-to-creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs. RESULTS: Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of the HTGP dogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs with HGTP compared to those without HGTP. No increased risk of hypertension, decreased antithrombin III activity, or cardiac disease was noted. Limited data from 8 dogs with HTGP showed no development of hypoalbuminemia or azotemia over a median follow-up period of 18 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Geriatric Miniature Schnauzers with HGTP may have a good prognosis overall, and are not typically azotemic or hypoalbuminemic.