Adult Nephropathy Research Articles

Healthcare Resource Use, Costs, and Disease Progression Associated with Diabetic Nephropathy in Adults with Type2 Diabetes: A Retrospective Observational Study.

IntroductionDiabetic nephropathy (DN) is a progressive kidney disease resulting as a complication of diabetes mellitus. This study evaluated the disease progression and economic burden of DN among commercially insured patients with type 2 diabetes in the USA.MethodsThe research design was a retrospective observational study based on healthcare claims data. The Truven MarketScan Databases (2004–2014) were queried for adults with type 2 diabetes with at least one urine albumin test (index, randomly selected) after diagnosis and at least one test after the index. On the basis of the index test, patients were classified into normoalbuminuria, microalbuminuria, or macroalbuminuria groups. Nephropathy-related treatment use was measured in the 6 months after the index, disease progression was assessed from the index to the end of data availability, and annual all-cause and nephropathy-related costs and healthcare resource use (HRU) were assessed up to 2 years from the index. Outcomes were compared between any two groups, controlling for baseline demographics.ResultsA total of 23,235 patients were identified and classified into normoalbuminuria (N = 18,409), microalbuminuria (N = 3863), or macroalbuminuria (N = 963) groups. Patients with albuminuria were more likely to be older, male, and have a higher burden of baseline comorbidities and HRU. Within 6 months following the index, 12–20% of patients with albuminuria were not treated with any relevant recommended treatment. Compared to the normoalbuminuria group, patients with macroalbuminuria had a significantly greater risk of disease progression (hazard ratio [HR] = 1.44), and both albuminuria groups were more likely to require dialysis (HR = 4.23 and 40.14 for micro- and macroalbuminuria, respectively; all p < 0.05). Annual all-cause (2016 US dollars, $3580 and $12,830 higher for micro- and macroalbuminuria vs. normoalbuminuria, respectively) and nephropathy-related ($362 and $3716) costs increased significantly with increasing nephropathy severity, consistent with the trend in increased HRU.ConclusionsDiabetic nephropathy may be undertreated or inappropriately treated. It was also associated with significantly higher costs, HRU, and risk of disease progression among commercially insured patients with type 2 diabetes in the USA.FundingTakeda Development Center Americas, Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0256-5) contains supplementary material, which is available to authorized users.

Effects of self-management support and family participation enhancing program for delayed progression of diabetic nephropathy in Thai adults with type 2 diabetes

Abstract Background/Purpose: Type 2 diabetes mellitus (DM) is increasingly becoming common in developing countries including Thailand. Uncontrolled hyperglycemia can lead to progression of severe complications for persons with DM which include diabetic nephropathy and can, later on, lead to kidney failure. Self-management support and participation of social groups, specifically the family of the patient, can help people with DM in controlling the complications of their disease from progressing; in this case, the advancement of diabetic nephropathy. The aim of this research is to develop a program and determine if self-management support with the participation of the family members will have an effect in delaying the progress of diabetic nephropathy in adults with type 2 DM. Theoretical Framework: Self-management based on social cognitive and self-regulation theories were used in this study to set a framework which utilizes social support from the family and self-efficacy of patients in implementing self-management activities. Methods: This is a quasi-experimental research. The sample consisted of 50 Thai adults with type 2 DM, 25 for the control group and 25 for the experimental group. The participants in the experimental group attended a self-management support and family participation enhancing the program for 8 weeks. The interventions included a video presentation, manual, and health education with a family member in a focus group. Data were collected before attending the program and evaluated on the 8th and 12 weeks after the program. The instruments used for the data collection were (1) Self-Management Activity Questionnaire (SMAQ), (2) Self- Efficacy Questionnaire (SEQ). The data collected for clinical outcome used the automatic physiological measures: Systolic and Diastolic blood pressure, Hemoglobin A1c (HbA1c), serum creatinine (SCr) and estimated glomerular filtration rate (eGFR). Data were analyzed using descriptive statistics, Independent t-test and Paired t-test and repeated measurement ANOVA. Results: The mean scores of the self-management activity and self-efficacy of the experimental group were significantly higher, their clinical outcomes for blood pressure, SCr and HbA1C levels were significantly lower, and eGFR results were significantly higher after attending the self-management support and family participation enhancing the program. Conclusions and Implications: The findings of this study indicate that the self-management and family participation enhancing program promote and support health behavior change and leads to better control of the delayed progression of diabetic nephropathy in Thai adults with type 2 DM. This can be applied by health care professionals in health care centers as a supplement to their usual care in dealing with persons with type 2 DM.

Membranous Nephropathy: The Journey Continues …

Membranous Nephropathy: The Journey Continues …

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

C4d immunohistochemistry in membranous nephropathy.

Background:Membranous nephropathy (MN) is the most common cause of nephropathy in adults. The diagnosis is based on characteristic light microscopic, electron microscope and immunofluorescence (IF) findings. In early MN, the light microscopic findings may be difficult to differentiate from minimal chain disease. In the absence of fresh frozen tissue for IF, immunohistochemistry with C4d aids in the diagnosis.Materials and Methods:A total 48 cases of MN diagnosed on renal biopsy were analyzed. The formalin fixed paraffin embedded tissues were stained with routine hematoxylin and eosin stains along with periodic acid-Schiff and silver methenamine stains to highlight the basement membrane. Fresh frozen tissues were available for IF in 40 cases. Immunostaining with C4d was done on paraffin-embedded sections by polymer-Horse Radish Peroxidase (HRP) technique using polyclonal antiserum to C4d (Biogenex, India).Results:There were 25 cases of idiopathic MN, 17 cases of Class V lupus nephritis and 2 cases were secondary to hepatitis C infection with cirrhosis. The glomerular basement membrane (GBM) was diffusely thickened with formation of spikes in 28 cases. In 11 cases the capillary loops were rigid but spikes were not seen and in 9 cases there was no apparent thickening of the basement membrane. All the cases showed diffuse positivity for C4d along the GBM.Conclusion:C4d is a reliable method to establish the diagnosis of MN and also a sensitive marker of complement activation reflecting the pathogenesis of MN.

99mTc-MAG3 Diuretic Renography in Diagnosis of Obstructive Nephropathy in Adults

The objective of this study was to compare 2 diuretic renography procedures: F-15 versus F+10(sp) for diagnosis of obstructive uropathy in adults. Thirty-six patients with unilateral or bilateral hydronephrosis had 2 consecutive Tc-MAG3 diuretic renograms within 7 days, using the widely used procedure F-15 in supine position, and a new seated-position procedure whereby the patient drinks 400 to 500 mL of water at 5 minutes and receives an injection of 20 mg of furosemide at 10 minutes [F+10 (sp)]. F-15 showed nonobstructive results in 63.9% of kidneys, obstruction in 26.4%, and equivocal findings in 6.9% and was not applicable in 2.8%. F+10(sp) showed nonobstructive results in 70.9%, obstruction in 27.8%, and equivocal result in 1.4% of kidneys. Nephroptosis was observed by F+10(sp) in 22.2% of kidneys. Adverse effects reported for the F-15 were hypotension in 2 patients, renal colic in 3 patients, and interruption due to voiding in 5 patients. No adverse effects were reported for F+10(sp). This study shows that the F+10(sp) procedure reduces the equivocal findings of F-15 procedure in 36 patients. It can improve the accuracy and compliance, avoiding adverse effects and reducing bladder filling-related problems.

Preventing the Harm of a Closer Look: Contrast-induced Nephropathy in Adults

Contrast media is administered to many patients in hospitals nationwide. Although the use of contrast and dyes is widespread and has a well accepted use among the medical profession, contrast-induced nephropathy can be a common and potentially harmful complication. Identifying patients at risk, attempting to minimize risk, and using preventative strategies should be priorities to decrease the harmful effects that are associated with the administration of contrast media. This article provides a general overview of contrast-induced nephropathy and a brief review of the risk factors and prophylactic treatment.

Immunoglobulin M nephropathy in adults and adolescents in India: A single center study of natural history

Immunoglobulin M nephropathy in adults and adolescents in India: A single center study of natural history

Glomérulopathies extramembraneuses idiopathiques et secondaires

Antibodies to neutral endopeptidase, a podocyte protein, are responsible for rare alloimmune neonatal membranous nephropathy that develops in children from neutral endopeptidase-deficient mothers. Neutral endopeptidase was the first podocyte antigen described in human membranous nephropathy. PLA2R1, the type-M receptor of soluble phospholipase A2, is a major target antigen in so-called idiopathic membranous nephropathy in adults. Antibodies to PLA2R1 are detected in 60 to 80% of patients before immunosuppressive treatment, and are only occasionally found in secondary membranous nephropathy. To date, they have not been detected in other pathological conditions and in healthy individuals. PLA2R1 and HLA-DQA1 gene variants defined by single nucleotide polymorphisms are strongly associated with idiopathic membranous nephropathy in patients of white ancestry, and can thus be considered as predisposing genes. In addition to their diagnostic value, anti-PLA2R1 antibodies can be used to monitor treatment. Immunization against cationic bovine serum albumin is a cause of early childhood membranous nephropathy. This finding points to a possible role of food and environmental antigens in membranous nephropathy. The newly identified antigen-antibody systems should be considered as molecular signatures challenging the uniform histological definition and having a major impact on patient care in a near future.

PLA2R Autoantibodies and PLA2R Glomerular Deposits in Membranous Nephropathy

To the Editor: Membranous nephropathy is a common cause of the nephrotic syndrome in adults. Treatment is controversial and challenging because of the heterogeneity of the disease and a lack of reliable biomarkers.1,2 M-type phospholipase A2 receptor (PLA2R) was recently identified as a major target antigen involved in idiopathic membranous nephropathy in adults.3 Circulating autoantibodies against PLA2R were found in 70 to 80% of patients with idiopathic membranous nephropathy but not in those with secondary membranous nephropathy or other renal diseases. It has been suggested that the serum level of PLA2R autoantibody . . .

Immunoglobulin M nephropathy nephropathy in adults and adolescents in India: A single-center study of natural history

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis (GN) usually presenting clinically as steroid resistant/dependent nephrotic syndrome (NS) with pathology of mesangial proliferative GN or focal and segmental glomerulosclerosis with diffuse predominant mesangial IgM deposits. Not much information is available about its natural history. This is the first Indian study to our knowledge on IgMN in adults and adolescents. We evaluated renal biopsies performed at our center between January,'04 to September,'09. Biopsies of all adolescents and adults were evaluated for IgMN and we studied their age, gender distribution, blood pressure (BP), disease duration, steroid/immunosuppressive management and serial serum creatinine (SCr), urinary proteins, and BP values. Patients with other systemic diseases/infections and children were excluded. IgMN constituted 4.3% of 2702 adult renal biopsies. No significant gender predilection was noted. Males presented at average age of 23.1 years, females at 30 years. Steroid-dependent NS was the commonest presentation noted in 75% followed by steroid-resistant NS. Hypertension was noted in 10% patients. Mesangial proliferative GN (MePGN) was commonest histopathological finding noted in 74.4%, followed by focal segmental glomerulosclerosis (FSGS) in 16.2%, and minimal change disease (MCD) in 9.4% biopsies. Sole IgM deposits were noted in 88.5%. All MCD, 35.6% MePGN reached remission, FSGS progressed to renal failure by 1 year. Hypertension, proteinuria, interstitial fibrosis, and FSGS were bad prognosticators. This is the first Indian study of IgMN in adults and adolescents carried out over a period of 5.8 years, which has shown that hypertension, proteinuria, and interstitial fibrosis at presentation have bad prognosis.

Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

OBJECTIVEFamilial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes.RESEARCH DESIGN AND METHODSTwenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring.RESULTSAll paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P = 0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05).CONCLUSIONSIn this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk.

Tonsillectomy with Methylprednisolone Pulse Therapy as Rescue Treatment for Steroid-Resistant IgA Nephropathy in Children

Primary immunoglobulin A (IgA) nephropathy is characterized by microhematuria and proteinuria and by the deposition of IgA in the glomerular mesangium. Steroid was a main drug for treatment of IgA nephropathy. However, some of children with IgA nephropathy are resistance to steroid treatment, but the therapy for steroid-resistant IgA nephropathy was not established. There have been reports on the efficacy of tonsillectomy as an initial treatment for IgA nephropathy in adults and children. We examined whether tonsillectomy with methylprednisolone pulse therapy (tonsillectomy pulse therapy) was effective as rescue treatment for steroid-resistant pediatric IgA nephropathy. We studied 11 patients (age at onset and duration of follow-up, 11.7 +/- 2.0 and 6.2 +/- 1.1 years) who had been diagnosed with steroid-resistant IgA nephropathy. Clinical features, laboratory data, and pathological findings were retrospectively compared between before and after tonsillectomy pulse therapy. Urinary protein excretion was significantly decreased at 24.7 +/- 7.3 months after tonsillectomy pulse therapy. On renal pathologic examination of 6 patients who underwent renal biopsy at 17.1 +/- 6.9 months after tonsillectomy pulse therapy, the activity index, an index of inflammation, was lower compared to the index evaluated before the therapy, but the chronic index, an index of renal sclerosis, remained unchanged. At 24.7 +/- 7.3 months after tonsillectomy pulse therapy, seven patients had normal urine and four had minor urinary abnormalities; namely, none had active renal disease or renal insufficiency. Our findings suggest that tonsillectomy pulse therapy may be effective as rescue treatment for steroid-resistant IgA nephropathy in childhood.

Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults

Progressive loss of kidney function complicates Fabry disease, an X-linked lysosomal storage disorder that arises from deficiency of alpha-galactosidase activity. Heterozygous females with Fabry disease can be as severely affected as hemizygous males, who have the classic form of the disease. Enzyme-replacement therapy with recombinant human alpha-galactosidase clears the glycosphingolipid globotriaosylceramide from kidney cells, and can stabilize renal function in adults with mild to moderate Fabry nephropathy. However, adults with more advanced nephropathy and overt proteinuria do not respond as well. For these patients, antiproteinuric therapy given in conjunction with enzyme-replacement therapy might prevent further decline in kidney function. In this Review, we propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults, based on published data and on the consensus of opinion of participants in the 7(th) International Fabry Nephropathy Roundtable in 2007. These organ-specific guidelines could be easier to implement than general guidelines, provided they are used in the context of an overall multisystem care approach.

ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy.

Radiation nephropathy has emerged as a major complication of bone marrow transplantation (BMT) when total body irradiation (TBI) is used as part of the regimen. Classically, radiation nephropathy has been assumed to be inevitable, progressive, and untreatable. However, in the early 1990's, it was demonstrated that experimental radiation nephropathy could be treated with a thiol-containing ACE inhibitor, captopril. Further studies showed that enalapril (a non-thiol ACE inhibitor) was also effective in the treatment of experimental radiation nephropathy, as was an AII receptor antagonist. Studies also showed that ACE inhibitors and AII receptor antagonists were effective in the prophylaxis of radiation nephropathy. Interestingly, other types of antihypertensive drugs were ineffective in prophylaxis, but brief use of a high-salt diet in the immediate post-irradiation period decreased renal injury. A placebo-controlled trial of captopril to prevent BMT nephropathy in adults is now underway. Since excess activity of the renin-angiotensin system (RAS) causes hypertension, and hypertension is a major feature of radiation nephropathy; an explanation for the efficacy of RAS antagonism in the prophylaxis of radiation nephropathy would be that radiation leads to RAS activation. However, current studies favor an alternative explanation, namely that the normal activity of the RAS is deleterious in the presence of radiation injury. On-going studies suggest that efficacy of RAS antagonists may involve interactions with a radiation-induced decrease in renal nitric oxide activity or with radiation-induced tubular cell proliferation. We hypothesize that while prevention (prophylaxis) of radiation nephropathy with ACE inhibitors, AII receptor antagonists, or a high-salt diet work by suppression of the RAS, the efficacy of ACE inhibitors and AII receptor antagonists in treatment of established radiation nephropathy depends on blood pressure control.

Evaluation on the effect of steroid therapy for the outcome of IgA nephropathy in adults on the basis of histological scoring: A clinicopathologic study of 104 cases

Application criteria of steroid therapy for the patients of IgA nephropathy (IgAN) have not yet been established. The purpose of the present study was to establish retrospectively the clinical and pathological criteria for the steroid therapy by using a histological scoring on 104 adult patients of IgAN. Steroid therapy was designated as an administration of prednisolone in the amount of more than 30 mg per day in the period of more than 4 weeks within 1 year of kidney biopsy.We developed our own scoring system for the following main glomerular and tubulointerstitial changes as shown in Table 1. The histological scoring was expressed by evaluating semiquantitatively the extent of glomerular and tubulointerstitial lesions in terms of activity index (AI) and chronicity index (CI). Activity index is the sum of graded score according to the extent of glomeruli with mesangial hypercellularity, intracapillary macrophagic infiltration and cellular crescent as well as to the extent of interstitial inflammation and tubulitis. Chronicity index is the sum of graded score according to the extent of glomeruli with global sclerosis, increase of extracellular matrices or periglomerular fibrosis, and tuft adhesion or fibrous (or fibrocellular) crescent as well as to the extent of interstitial fibrosis (Table 1). Histological scoring Score 0 1 2 3 AI: Activity Index G: glomerular m: mesangial hypercellularity − &lt; 40% &lt; 80% ≥ 80% i: intracapillary macrophage infiltration − + ++ e: cellular crescent 0 &lt; 30% ≥ 30% I: tubulointerstitial i: interstitial inflammation − + ++ t: tubulitis − + ++ CI: Chronicity Index G: glomerular s: global sclerosis &lt; 10% &lt; 30% &lt; 50% ≥ 50% i: increase of extracellular matrix &lt; 10% &lt; 30% &lt; 50% ≥ 50% e: fibrous (or fibrocellular) crescent, adhesion &lt; 10% &lt; 30% &lt; 50% ≥ 50% I: tubulointerstitial interstitial fibrosis &lt; 10% &lt; 30% &lt; 50% ≥ 50% AI: AGm + AGi + AGe*2 + AIi + Ait, CI: CGS + CGi + CGe + CI For the applicability of steroid therapy, three groups were categorized by evaluating the statistical significance for the correlation of AI, CI and daily amount of urine protein to the outcome of the patients as follows (Table 2). In group A (inappropriate indication of steroid therapy) which showed CI ≥ 5 alone, 10 out of 11 cases revealed decline of renal function (Cr ≥ 1.2 mg/dL and Ccr &lt; 80 mL/min) within 2.2–19.3 years (mean 9.0 ± 6.4 years) without respect to steroid therapy. In group B (unnecessary indication of steroid therapy) which showed CI &lt; 5, AI &lt; 5, and UP &lt; 1 g/day, 58 out of 60 cases showed normal renal function (Cr &lt; 1.2 mg/dL and Ccr ≥ 80 mL/min) within 4.2–21.6 years (mean 10.1 ± 4.7 years). In group C (necessary indication of steroid therapy) which showed CI &lt; 5 and AI ≥ 5 or UP ≥ 1 g/day, patients with steroid therapy revealed significantly higher incidence of outcome with normal renal function (12 out of 13 patients, final evaluation of renal function in 6.8 ± 2.3 years after renal biopsy) than that of the patient without steroid therapy (seven out of 20 cases, evaluation of renal function in 9.2 ± 4.0 years after renal biopsy) (P &lt; 0.01) (Table 3). In the 13 patients with steroid therapy in group C (steroid pulse in four patients, prednisolone 40 mg/day internally in three patients, predonisolone 30 mg/day internally in six patients) showed a significant decrease of proteinuria and remained until final evaluation time (Table 4). Application criteria of steroid therapy image Comparison of steroid (−) with steroid (+) in the group of ‘necessary’ steroid therapy + − P no. 13 20 At Renal Biopsy age (years) 31.5 ± 12.9 36.3 ± 13.0 ns UP (g/day) 2.3 ± 1.9 1.3 ± 0.5 &lt; 0.05 Cr (mg/dL) 0.8 ± 0.3 0.9 ± 0.1 ns CCr (mL/min) 111 ± 43 92 ± 34 ns Hypertension (n) 1 9 ns + ACEI (n) 4 10 ns Follow‐up years from renal biopsy 6.8 ± 2.3 9.2 ± 4.0 ns End of follow‐up Cr (mg/dL) 0.8 ± 0.3 5.5 ± 6.6 &lt; 0.01 Normal renal function (n) 12 7 Renal insufficiency (n) 1 6 &lt; 0.01 Dialysis (n) 0 7 Change of urine protein in the 13 cases with steroid treatment in the group of 'necessary' image From the results above, our evaluation system using histological scoring together with grading proteinuria was proven to be useful in estimating the applicability of steroid therapy for adult IgAN patients.

Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux--radiological and pathoanatomical analysis.

To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage.

Outcome of IgA nephropathy in adults graded by chronic histological lesions

This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 μmol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.

Urinary excretion of albumin in adolescents with type 1 diabetes: persistent versus intermittent microalbuminuria and relationship to duration of diabetes, sex, and metabolic control.

Urinary excretion of albumin is a marker for incipient diabetic nephropathy in adults. The intra-individual variability, as well as the relationship to duration of diabetes, onset of the disease, and long-term metabolic control, have not been evaluated in a large sample of pediatric patients. A total of 5,722 nocturnal urinary albumin excretion rates were determined in 447 children, adolescents, and young adults with type 1 diabetes, comprising 1,821 years of observation. Excretion rates were related to duration of diabetes, age at onset of diabetes, sex, blood pressure, and metabolic control. Based on repeated measurements in individual patients, the positive predictive value of one sample was 76%, the negative 99.5%. After a duration of diabetes of 11 years, 5% of patients displayed persistent microalbuminuria (10% after 13 years). The duration of diabetes until persistent microalbuminuria was identical for patients with prepubertal or pubertal onset of diabetes. In addition to duration, female sex (P < 0.03) and insufficient long-term metabolic control (P < 0.03) contributed significantly and independently to urinary albumin excretion. Determination of urinary albumin excretion rate is useful in pediatric patients. Female subjects with a long duration of diabetes and insufficient metabolic control are especially at risk for microalbuminuria. Even if persistent microalbuminuria usually becomes evident in patients aged > 11 years, the prepubertal duration of diabetes contributes equally to this risk. Good metabolic control therefore should be aspired to from the onset of diabetes.

Clinicopathological study of IgA nephropathy in adults: The influence of onset age on clinical and renal histological findings and on the effect of steroid therapy

Background. The prognosis of IgA nephropathy (IgAN) varies according to the patient's age. It usually affects children or young adults. However, the onset age for IgAN may be at middle-age or older. The influence of onset age on the clinical and renal histological findings of adult IgAN was investigated. Methods. We selected 39 IgAN patients in whom renal biopsy was performed within 2 years from the onset. The patients were divided into two groups according to onset age; early-onset group (under 35 years; group E) and late-onset group (over 35 years; group L). The clinical and histological findings and the response to steroid therapy were compared in the two groups. Results. (1) Clinically, the levels of proteinuria and hematuria in groups E and L were not different, but the creatinine clearance was lower in group L than in group E. Hypertension was frequent in group L (66.7%), but not in group E. (2) Histologically, the rate of glomerular obsolescence and the grades of interstitial fibrosis and arterio- and arteriolosclerosis were more advanced in group L than in group E. However, there were no differences in the grade of mesangial cell proliferation or mesangial matrix increase, nor were the rates of glomerular crescent and tuft adhesion formation different between the two groups. (3) The reduction of proteinuria and hematuria after 1-year steroid therapy was similar in the two groups. Conclusion. Onset age does not affect the severity of glomerular lesions and the effect of steroid therapy in the early phase of adult IgAN. However, advanced interstitial fibrosis and arterio- and arteriolosclerosis, which may be related to hypertension or the aging process, lead to impaired renal function in late-onset IgAN patients.