Pattern Of Proteinuria Research Articles

Electrophoretic patterns of proteinuria in feline spontaneous chronic kidney disease.

The purpose of this study was to describe the electrophoretic patterns of proteinuria in cats at risk of and cats with chronic kidney disease (CKD), and to investigate whether the presence of high-molecular-weight (HMW) and low-molecular-weight (LMW) proteins were associated with CKD, proteinuria and/or disease progression. Healthy cats at risk of developing renal disease (n = 17) and cats affected with CKD at different stages (n = 22) were prospectively enrolled and sampled over time. Seventy urine samples were included and assayed with a commercially available sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) method. Each sample (gel lane) was inspected to identify albumin, HMW and LMW proteins, and an electrophoretic pattern (albuminuria, glomerular, tubular, mixed or negative) was assigned accordingly. Fisher's exact test was used to assess the distribution of HMW and LMW proteins in cats grouped according to International Renal Interest Society stage and to the magnitude of proteinuria, and to assess if HMW and LMW proteins at the time of inclusion were associated with the development and progression of CKD. In samples of cats at risk, the most common pattern was glomerular (84.6%); glomerular pattern was also common in cats with CKD (54.2%), although mixed proteinuria and tubular proteinuria were also present (29.5% and 11.4%, respectively). The presence of LMW proteins was associated with CKD (P <0.0001) and to a urine protein:creatinine ratio >0.2 (P = 0.025). Both HMW and LMW proteins were not associated with progression of CKD within 6 months (n = 14). Our results showed that HMW proteinuria is common in healthy cats at risk of developing CKD, although the pathological significance needs to be confirmed. The detection of LMW proteins in urine of cats suspected to be affected by CKD, especially in non-azotaemic, non-proteinuric or borderline proteinuric cats, suggests the presence of kidney damage.

Febrile Proteinuria in Hospitalized Children: Characterization of Urinary Proteins.

Background: Transient proteinuria during febrile illness is a common phenomenon. Recent studies have re-examined the pathophysiology of proteinuria and new urinary markers to characterize it, including B7-1 (CD80), which is expressed also in glomerular podocytes and influences the glomerular barrier.Aim: To investigate the pattern of proteinuria in febrile non-renal diseases, including B7-1.Methods: We prospectively analyzed urine samples of 44 febrile children and 28 afebrile controls for different protein components: albumin (glomerular marker), β2-microglobulin (tubular marker), uromodulin (Tamm Horsfall protein-THP, a renal endogenous protein) and B7-1. Febrile illness was characterized as focal bacterial vs. viral. Exclusion criteria were underlying renal disease, steroid treatment or urinary tract infection.Results: Elevated urine albumin (64.5 ± 10.3 vs. 17.8 ± 4 mg/g, mean ± S.E.M., p = 0.0009) and β2-microglobulin (1.44 ± 0.34 vs. 0.182 ± 0.03 mg/g, mean ± S.E.M., p = 0.005] and decreased uromodulin (10.5 ± 1 vs. 26.7 ± 2.2 Arbitrary units, mean ± S.E.M., p = 0.0001) excretion were found during febrile illness vs. controls. Urine B7-1 was also increased in the febrile group (0.27 ± 0.05 vs. 0.07 ± 0.01 ng/ml, mean ± S.E.M., p = 0.001), and was the only marker which was significantly higher in bacterial vs. viral disease.Conclusions: Febrile proteinuria is not generalized: while proteins of both glomerular and tubular origin increase, uromodulin decreases. Urine B7-1 is increased during fever, more significantly in bacterial infections. Thus, urinary B7-1 may be used as an additional marker to differentiate between febrile states of bacterial vs. viral origin.

Use of urinary γ-glutamyl transferase (GGT) to monitor the pattern of proteinuria in dogs with leishmaniasis treated with N-methylglucamine antimoniate

The aim of this study was to assess if the coupled analysis of the urinary protein to creatinine (UPC) ratio and of the GGT/UC ratio (the ratio between urinary γ-glutamyl transferase activity and urinary creatinine) may be used in treated leishmaniotic dogs to differentiate dogs with transient impairment of tubular function from dogs with persistent tubular damage.To this aim, 40 urine from 10 proteinuric and leishmaniotic dogs that at the first visit had high GGT/UC ratio, consistent with tubular damage, were collected and analyzed before treatments and 2, 4 and 6 weeks after treatment with N-methylglucamine antimoniate and allopurinol.Compared with pre-treatment values, at the end of the study period the UPC ratio decreased only in 5/10 dogs, which, however, were still proteinuric or borderline proteinuric. Conversely, the GGT/CU ratio decreased in 8/10 dogs and in 3 of them the values at the end of the study period were below the threshold consistent with tubular proteinuria. The GGT/UC values at 6 weeks was significantly lower than before treatment. However, transient increases were frequent for both the analytes.These results indicate that in most of the dogs that remain proteinuric after treatment, likely due to the persistent glomerular damage, the GGT/UC ratio tends to normalize. This suggests that in these dogs tubular proteinuria at admission depends on functional impairment of tubular cells likely due to the overflow of proteins from damaged glomeruli. However, tubular proteinuria occasionally persists, suggesting that tubulointerstitial damages persist even in dogs responsive to treatments.

Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate.

The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100-500mg/g creatinine) among HIV-positive adults. Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed. Among 411 patients, 18 (4.4%) presented albuminuria>300mg/g creatinine and/or proteinuria>500mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1%) had no significant proteinuria or albuminuria (<100 and<30mg/g creatinine, respectively), 60 (15.3%) had moderate albuminuria, while 152 (38.7%) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir<500/µl, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR). We detected significant proteinuria in 230 (56.0%) of 411 HIV-positive patients. Among this group, 152 (66.1%) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed.

Nonalbumin proteinuria predominates in biopsy-proven tenofovir nephrotoxicity

Tenofovir disoproxil fumarate (TDF) nephrotoxicity is characterized by proximal renal tubular injury and dysmorphic mitochondria resulting in proteinuria, orthoglycemic glycosuria, and other markers of proximal tubular dysfunction. The objective of this study was to determine the pattern of proteinuria in patients with biopsy-proven TDF nephrotoxicity. Retrospective chart review. Patients with biopsy-proven TDF nephrotoxicity were identified and their medical charts and biopsy reports were reviewed. Comparison was made with HIV-infected patients not on TDF who underwent kidney biopsy. We identified 43 biopsy-proven cases of TDF nephrotoxicity; mean age 54.7 ± 0.4 years, 53% men, 42% whites. Thirty-seven cases reported proteinuria by dipstick of which only 60% had at least 2+ proteinuria. Twenty-seven patients had urine protein quantified by either 24-h collection or spot urine protein-to-creatinine ratio; median proteinuria was 1742 mg/day [interquartile range (IQR) 1200-2000 mg] and 1667 mg/g creatinine (IQR 851-1967 mg/g), respectively. Ten patients had concurrent urinary albumin measured, with a median 236 mg/g creatinine (IQR 137-343 mg/g). The mean urine albumin-to-urine protein ratio (uAPR) was 0.17 (IQR 0.14-0.19), confirming that TDF nephrotoxicity is primarily associated with nonalbumin proteinuria. Control cases had a uAPR of 0.65 (IQR 0.55-0.79) P < 0.001. Histopathology showed the predominance of proximal tubular injury with characteristic mitochondrial abnormalities. In the largest published cohort of patients with biopsy-proven TDF nephrotoxicity, we show that low uAPR is a reliable feature of this disease. Because of the predominance of nonalbumin proteinuria, dipstick urinalysis may be unreliable in TDF nephrotoxicity.

Urinary albumin to protein ratio: more of the same or making a difference?

In this issue, Smith et al. [1] consider whether the simple ratio of urine albumin to total protein (uAPR) provides a measure of low molecular weight (LMW) proteinuria that distinguishes tubular versus glomerular pathology. In a retrospectively studied cohort of 1011 proteinuric patients [protein:creatinine ratio (PCR) >30 mg/mmol], uAPR was correlated with simultaneous findings on urine protein immunofixation electrophoresis (uPEI). A single, blinded observer categorized the electrophoresis pattern as being either tubular (predominantly LMW), glomerular (a dominant albumin band), mixed or overflow (light chain monoclone) proteinuria. The LMW protein b2-microglobulin (b2M) and the tubular enzyme N-acetyl-b-D-glucosaminidase (NAG) were also measured in a subgroup (n ¼ 248) of outpatients and their predictive performance at uPEI classification compared to that of uAPR. Renal biopsy results were available to confirm the diagnostic utility of uAPR for only 68 patients. uAPR gave a reasonable prediction of a ‘tubular’ uPEI proteinuria pattern in ROC curve analysis (AUC 0.84), which was similar to that of b2M and NAG. It also performed better than albuminuria alone in differentiating primary tubular versus glomerular pathology confirmed on biopsy. Clearly, measurement of urine protein leak is central to the detection, diagnosis, prognosis and treatment of kidney disease. Most guidelines currently recommend the measurement of an early morning spot urine for either albumin:creatinine ratio or protein:creatinine ratio. In general, lowlevel albuminuria/proteinuria is considered reflective of vascular or tubulointerstitial renal pathology, while higher levels (>1 g/g � 1 g/24 h) are thought to reflect underlying glomerular pathology. Such interpretation is rather simplistic and frustrating in view of the ready availability of urine for more extensive analysis and interpretation. With the exception of haematology, no other specialty has easy access to a body fluid so closely related to the function of the organ for which it is responsible. Interpretation of raised urine protein level is confounded by the various inter-related factors that influence its excretion (Table 1). These include glomerular factors affecting filtration, tubular factors controlling reabsorption of filtered proteins and vascular influences both at the glomerular and peritubular level. Consequently, the excreted urine protein is seldom the simple result of a well-defined pathology; instead, it mirrors complex glomerular, tubular and vascular interactions. Furthermore, excessively filtered/re-absorbed protein has been implicated for the last 20 years in the pathogenesis of glomerular and tubulointerstitial sclerosis, respectively [2, 3], thus potentially aggravating the very processes that contribute to its leakage. Previous investigations of the clinical implications of urine protein profiles have categorized leaked plasma proteins as low, intermediate or high molecular weight (MW)

The value of simultaneous measurements of urinary albumin and total protein in proteinuric patients

Proteinuria is a common pathological finding in renal disease. Examining the urinary protein electrophoretic pattern gives clues to the site of origin of the protein. We hypothesized that the type of proteinuria, classified by urine protein electrophoresis and immunofixation (uPEI), may be predicted by simply examining the proportion of higher molecular weight protein (e.g. albumin) in urine total protein content. One thousand and eleven patients, whose urine had been sent to the pathology department for uPEI, were analysed for total protein and albumin to creatinine ratio (uPCR and uACR) and the ratio reported as the albumin to total protein ratio (uAPR). In a group of renal outpatients (n=248), we also specifically measured tubular proteins (N-acetyl-β-D-glucosaminidase, NAG, and β2-microglobulin) and expressed these as ratios to creatinine (uNCR and uβ2CR). To validate these findings, we correlated these measurements with 68 patients in whom we also had renal biopsy data. In receiver operating characteristic (ROC) curve analysis, the AUC for uAPR was 0.84 for predicting tubular proteinuria pattern on uPEI. In the renal outpatient subgroup, uAPR predicted a tubular pattern of urinary protein equally as well as testing for specific tubular protein markers (uNCR and uβ2CR). In the validation cohort, a uAPR cut-off of <0.40 was 88% sensitive and 99% specific for the diagnosis of primary tubulointerstitial disorders on renal biopsy. Useful information about the origins of urinary protein may be inferred by measuring uAPR, the measurement of which is both simple and inexpensive.

Quantitative and Qualitative Urine Protein Excretion in Dogs with Severe Inflammatory Response Syndrome

Proteinuria is an established characteristic of renal disease in dogs, providing diagnostic and prognostic information. Little is known about the occurrence and severity of proteinuria in dogs with severe inflammatory response syndrome (SIRS). The quantitative and qualitative urinary protein (UP) excretion is altered in dogs with SIRS. Thirty-nine dogs with SIRS and 15 healthy control dogs at admission. A case control study was performed. Diagnosis of SIRS was based on clinical and clinicopathological findings. Urinary protein (UP) was measured by a colorimetric assay. Urinary albumin (UAlb) and urinary retinol-binding protein (URBP) were measured by ELISA and quantified in relation to urinary creatinine (UC). Sodium dodecyl sulfate polyacrylamid-gel electrophoresis was conducted to identify the qualitative pattern of proteinuria. Mann-Whitney U-test was used to assess differences in UP/UC, UAlb/UC and URBP/UC between the groups. P-values < .05 were considered significant. Dogs with SIRS had higher ratios of UP/UC, UAlb/UC and URBP/UC (all P < .001) in comparison to healthy control dogs. Dogs with SIRS had a total of 11 protein bands compared to 3 bands in healthy controls. In dogs with SIRS, 58% of the total counted bands were in the low molecular weight range (<60 kDa) whereas 42% were in the middle (60-80 kDa)/high molecular weight range (>80 kDa). SIRS alters UP excretion in dogs. Further studies should evaluate whether or not the magnitude of proteinuria is predictive of the severity and outcome of dogs with SIRS.

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy.

BackgroundIsolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.MethodsData from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.ResultsHigher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.ConclusionsEstablished pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.

Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study

Proteinuria is an important complication in renal transplant recipients. The aim of this prospective study was to evaluate the long-term impact of transplant proteinuria patterns on allograft function and survival. We analyzed urinary protein of a cohort of 83 renal transplants with proteinuria ≥0.5 g/d by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radial immunogel diffusion assay. After initial stratification and analysis, the cohort was followed up for 16 yr. The graft outcome and survival were analyzed using Cox regression model to determine their association with different patterns of initial transplant proteinuria. Group with predominantly glomerular (middle- and high-molecular-weight with or without low-molecular-weight) proteinuria (61%) had higher serum creatinine (p < 0.001) than the group with predominantly tubular (low-molecular-weight) proteinuria (39%). The incidences of chronic graft dysfunction and graft loss had increased in the glomerular proteinuria group (p < 0.001, hazard ratio 3.6, 95% confidence interval 1.7-7.5 and p < 0.001, hazard ratio 4.9, 95% confidence interval 1.9-12.1, respectively). Patient death did not differ (p = 0.434, hazard ratio 1.5, 95% confidence interval 0.5-4.5). Proteinuria in renal transplants can be differentiated into glomerular and tubular types based on molecular weight. Glomerular proteinuria is associated with significant increase in graft dysfunction and graft loss.

Proteinuria in Patients with Thrombotic Thrombocytopenic Purpura

The kidney is a target organ in thrombotic thrombocytopenic purpura (TTP), but the pattern of proteinuria has been poorly described. We retrospectively analyzed proteinuria in all 59 patients with a diagnosis of TTP on their discharge summary from 2000 to 2009. Urinalysis was obtained in 89% of cases; in these, proteinuria was detected by urine dipstick in 85%. In patients with dipstick proteinuria, quantification (grams per day or grams per gram creatinine) was performed in only 34% and ranged from 0.16 grams to 8.0 grams. Patients with larger amounts of proteinuria had more severe acute renal failure, were more likely to receive a renal biopsy, and were more likely to undergo dialysis. When analysis was restricted to patients with highly depressed activity levels of the metalloprotease ADAMST13, proteinuria tended to be low-grade and transient, and renal insufficiency was mild. Proteinuria is common in thrombotic microangiopathies and may be nephroticrange, but TTP with depressed ADAMST13 activity is characterized by less proteinuria and less severe renal dysfunction. Although this study presents the largest sample of proteinuria quantification ever reported for TTP, quantification was performed in only one-third of cases.

The pattern of proteinuria following karate (Kumite) competitions.

Sir, Despite the large amount of proteins in the plasma, the urine is virtually protein free due to the selectivity of the glomerular barrier [1]. The major component of urinary protein is a tubular protein (Tamm-Horsfall) while albumin constitutes 30–40% of the total urinary protein. Various physiologic settings, including exercise, can induce a transient increase in the urinary protein excretion that is usually benign and reversible. The type of post-exercise proteinuria depends on the intensity of exercise rather than its duration, so that moderate exercise induces glomerular and heavy exercise glomerular-tubular mixed-type protein loss [2]. Post-exercise proteinuria may be due to the loss of the charge selectivity from the glomerular capillary wall, a relative preservation of the glomerular filtration rate, proteinuria out of proportion of maximal tubular reabsorption capacity following heavy exercise [2,3] and oxidative stress produced by free radicals due to enhanced oxygen consumption in muscles [4]. The purpose of our study was to compare the amount and pattern of proteinuria before and after karate (Kumite) competition in 18 male practitioners, aged 18–21 years, with similar physical characteristics. All practitioners competed in three rounds, each lasted 3 min, with a 10 min resting interval between them. Urine samples were collected just before the competition and during 24 h thereafter. Total urinary protein, urinary beta2-microglobulin B2M as tubular and albumin as glomerular protein were assayed. Before competition, the mean value of total urinary protein, albumin and B2M as basal levels were 70.68 ± 12.5, 4.84 ± 3.17 and 0.0217 ± 0.0133 mg/day, respectively. After competition, the mean values of 24-h total urine protein (196.05 ± 70.88 mg/day), albumin (34.07 ± 32.88 mg/day) and B2M (0.0933 ± 0.0372 mg/day) levels were significantly increased (P = 0.023, P = 0.001 and P < 0.001). This study revealed significantly increased proteinuria of a mixed type (albumin and B2M) in all practitioners following exhaustive short-term competition. Despite the mixed type of proteinuria, we observed a six-fold increase compared to the basal level in urine albumin (versus four-fold increase for urinary B2M) suggesting a more prominent role of glomerular proteinuria probably due to glomerular membrane permeability changing factors, such as sympathetic overactivity and competitive stress. Conflict of interest statement. None.

Relationship between circadian blood pressure variation and circadian protein excretion in CKD

Circadian blood pressure changes are blunted in patients with chronic kidney disease (CKD). Proteinuria is the most important correlate of hypertension in CKD. However, little is known about the influence of circadian blood pressure changes and variation in protein excretion rate. Furthermore, the impact of blood pressure components, e.g., mean arterial pressure and pulse pressure, on proteinuria has not been evaluated. To analyze the relationship of circadian changes in blood pressure on urinary protein excretion patterns, glomerular filtration rate was measured with iothalamate clearance and 24-h ambulatory blood pressure with SpaceLabs 90207 monitor in 22 patients with CKD. It was found that hourly protein excretion rates were 31% higher during the night. Excretion results of sodium, potassium, chloride, urea, and creatinine were also between 30 and 40% higher at night. Systolic, mean arterial, and pulse pressures but not diastolic pressure were related to daytime protein excretion rate. At night, the relationship of systolic, diastolic, and mean arterial pressures was significantly lower and essentially flat with respect to protein excretion rate, but the relationship of pulse pressure and proteinuria was not different from that seen during the day. Circadian variation in blood pressure did not impact circadian sodium excretion rate. In conclusion, these data suggest that patients with CKD have patterns of proteinuria that share different relationships with blood pressure components depending on the awake-sleep state. Pulse pressure is related to proteinuria independent of the awake-sleep state. Reducing mean arterial pressure during the day and pulse pressure during the day or night may be effective antiproteinuric strategies.

Absence of Increased α1-Microglobulin in IgA Nephropathy Proteinuria

To search for biomarkers of IgA nephropathy, protein profiles of urine samples from patients with IgA nephropathy and normal volunteers were compared using two-dimensional DIGE. Most of the 172 spots identified in the urine were serum proteins, and their amounts in IgA nephropathy urine were much higher than those in normal urine; this can be explained as proteinuria caused by glomerular dysfunction. However, only alpha(1)-microglobulin, also one of the major serum proteins, in IgA nephropathy urine was not higher in amount than that in normal urine. We confirmed using ELISA analysis that the amounts of transferrin and albumin in IgA nephropathy and diabetic nephropathy urine were much higher than those in normal urine, whereas the amount of alpha(1)-microglobulin in IgA nephropathy urine was not higher than that in normal urine and was much lower than that in diabetic nephropathy urine. Approximately 50% of alpha(1)-microglobulin forms a complex with IgA in serum. These results suggest that alpha(1)-microglobulin in IgA nephropathy urine is a characteristic protein and might be a biomarker for IgA nephropathy and that alpha(1)-microglobulin might have a relationship with IgA nephropathy pathology.

3rd College of Physicians’ Lecture – Translational Research: From Bench to Bedside and From Bedside to Bench; Incorporating a Clinical Research Journey in IgA Nephritis (1976 to 2006)

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.

Comparison between 24‐h proteinuria, urinary protein/creatinine ratio and dipstick test in patients with nephropathy: Patterns of proteinuria in dipstick‐negative patients

Objective. Three main tests are commonly employed for the measurement of proteinuria: the dipstick test, the urinary protein/creatinine ratio (P/C) and the 24‐h urine collection. The aim of this study was to evaluate the correlation between these methods, comparing linear regression and ROC curve data. Material and methods. A total of 297 consecutive outpatients with different renal diseases were included in the study. Twenty‐four‐hour proteinuria was considered the reference test. Results. A high degree of correlation was observed between all the tests (p<0.0001), the highest regression coefficient being between 24‐h proteinuria and P/C (R = 0.82), and the lowest between P/C and the dipstick test (R = 0.72). The dipstick test failed to detect pathological proteinuria in 94 patients (31.6 %). Therefore, in these subjects, the patterns of proteinuria were assessed by immunofixation and sodium dodecyl sulphate (SDS) electrophoresis. Conclusions. Our data strongly support the use of urinary P/C for the detection of proteinuria, at least in nephrology units, where the prevalence of proteinuria is likely to be high.

The Grafted Kidney Takes Over: Disappearance of the Nephrotic Syndrome After Preemptive Pancreas-Kidney and Kidney Transplantation in Diabetic Nephropathy

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.

Complete reversal of the nephrotic syndrome after preemptive pancreas-kidney transplantation: a case report

BackgroundNephrotic syndrome due to diabetic nephropathy is presently considered an indication for pancreas-kidney transplantation even in the absence of severe renal failure. Reversal of the nephrotic syndrome has been reported, but the mechanisms of this effect are unclear. AimTo describe the renal morphofunctional pattern and the pattern of proteinuria before and after preemptive pancreas-kidney transplantation. MethodsMethods included quantitative and qualitative assessment of proteinuria as well as renal ultrasound and scintiscan. Case reportA 42-year-old woman with type 1 diabetes since age 24 had widespread end-organ damage. Renal biopsy (2001) showed a mainly nodular pattern of diabetic nephropathy. Following referral (1999), her serum creatinine ranged from 1.6 to 2.2 mg/dL, with nephrotic range proteinuria (glomerular nonselective, tubular complete). Renal scintiscan revealed bilateral, symmetric, well-perfused kidneys. The functional data before pancreas-kidney graft (February 2003) were: serum creatinine 1.6 mg/dL, creatinine clearance 58 mL/min, serum albumin 2.6 g/dL, proteinuria 9.1 g/d. At hospital discharge (March 2003), the creatinine was 1.2 mg/dL, the creatinine clearance 97 mL/min, the proteinuria 0.676 g/d. Two months later, the creatinine was 1.2 mg/dL and proteinuria 0.421 g/d. A renal scintiscan demonstrated the functional prevalence of the grafted kidney (77% of total function), with vital, almost completely excluded native kidneys (functional contribution, 11.5% each). Proteinuria, ranging from 0.3 to 0.6 g/d, showed a physiological pattern. ConclusionsFunctional exclusion of the native kidneys by renal scintiscan gives morphological support to reversal of the nephrotic syndrome.

Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?

Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

Proteinuria after injection of human focal segmental glomerulosclerosis factor.

Recurrent focal segmental glomerulosclerosis (FSGS) is heralded by proteinuria that may remit after treatment with plasmapheresis or immunoadsorption. Study of recurrent FSGS has been hampered by lack of an animal model that exhibits a pattern of proteinuria that mimics human disease. We have obtained a component of FSGS patient plasma (FSGS factor) that increases glomerular albumin permeability (P(alb)) in vitro and causes transient proteinuria in vivo. Plasma fractions containing FSGS factor and comparable plasma fractions from normal donors were injected into normal male Sprague-Dawley rats. Urinary protein, albumin, and creatinine were measured at various time points. Additionally, plasma samples from test animals were collected after injection and tested for FS activity defined by increased P(alb). Finally, glomeruli were isolated from animals after injection and P(alb) of these glomeruli tested. Proteinuria and albuminuria were increased by 24 hr after injection with FSGS factor, and returned to baseline by 48 hr after injection. Injection with the same fraction of normal plasma had no effect on urinary protein. FSGS factor increased urinary protein in a dose-dependent manner. Serum collected from rats 15 or 60 min after injection with FSGS factor increased P(alb) of glomeruli in vitro, whereas serum collected 3 or more hours after injection had no effect. Glomeruli isolated from rats receiving injections with FSGS factor had increased in vitro P(alb) compared with glomeruli from rats injected with a fraction from normal plasma. We have demonstrated that a single injection of FSGS factor increases P(alb) and, causes transient albuminuria and proteinuria in rats. FS activity in the plasma of recipient rats is also transient. This is the first detailed description of the time course and dose-dependence of proteinuria caused by FSGS factor in an animal model.