The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China

OBJECTIVE: This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001) was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria ‘thresholds’ of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin-to-creatinine ratio and 24-hour proteinuria were associated with renal outcomes in univariate analyses. CONCLUSION: This study supports the recommendation of using the albumin-to-creatinine ratio, rather than 24-hour proteinuria, to monitor proteinuria and prognosis in primary IgA nephropathy.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy / Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria more than 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 more or less 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 more or less 1.86 g/day; serum creatinine 1.07 more or less 0.29 mg/dl; mean follow-up 60.10 more or less 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 more or less 0.07 g/day (P less than 0.001) while serum creatinine did not vary: 1.07 ± 0.28 mg/dl (P=ns). After a mean follow-up of 42.36 more or less 21.56 months urinary protein excretion (0.12 more or less 0.06 g/day) and renal function (serum creatinine 1.06 more or less 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to less than 0.5 g/day in patients with IgA nephropathy without changes in renal function.

El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias major que 0.5 g/día y creatininas séricas menor que 1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a menor que 0.5 g/día. Fueron incluidos 20 pacientes: Edad: 37.45 más o menos 13.3 años (50% hombres); 7 pacientes (35%) eran hipertensos; proteinuria inicial 2.2 más o menos 1.86 g/día; creatinina inicial 1.07 más o menos 0.29 mg/dl; seguimiento promedio: 60.10 más o menos 31.47 meses (5 más o menos 2.62 años). La nefropatía por IgA fue subclasificada según Haas: 12 pacientes (60%) clase II; 7 (35%) clase III y 1 (5%) clase V. Todos recibieron enalapril más valsartán según tolerancia más metilprednisona vía oral en dosis de 0.5 mg/kg/día durante las primeras 8 semanas y subsecuentemente se redujo cada dos semanas hasta llegar a 4 mg. Se discontinuaron los esteroides luego de 24 semanas (6 meses). La inhibición del sistema renina angiotensina prosiguió indefinidamente. A las 10 semanas la proteinuria disminuyó de 2.2 más o menos 1.86 g/día a 0.15 más o menos 0.7 g/día (p menor que 0.001); la creatinina no varió significativamente (1.07 más o menos 0.29 mg/dl vs. 1.07 más o menos 0.28 mg/dl) (P=ns). Luego de 10 semanas y con un seguimiento de 42.36 más o menos 21.56 meses la proteinuria (0.12 más o menos 0.006 g/día) y la función renal (creatinina 1.06 más o menos 0.27mg/dl) permanecieron estables. No se informaron efectos adversos durante el estudio. El doble bloqueo del sistema renina angiotensina más bajas dosis de metilprednisona resultó útil para reducir...

Additive Antiproteinuric Effect of Combination Therapy with ACE Inhibitor and Angiotensin II Receptor Antagonist: Differential Short-term Response between IgA Nephropathy and Diabetic Nephropathy

In previous studies, the synergistic antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists (ATRAs) has been inconsistent in relation to underlying renal diseases. The influence from the blood pressure (BP) - reducing effect in some studies might also contribute to this inconclusiveness. To examine the possibility of the benefit being different according to underlying renal diseases, we undertook a crossover therapeutic trial of the combination therapy in two selected homogenous groups of patients with diabetic and non-diabetic renal diseases. The BP-reducing effect was excluded during the study. Nineteen biopsy-proven IgA nephropathy, as examples of non-diabetic renal diseases, and 24 type 2 diabetic nephropathy patients were selected as the study subjects. The subjects had to meet the follow criteria: a creatinine clearance (Ccr) between 25 - 90 ml/min/1.73 m2, 24-hr urinary protein excretion rate over 1.0 g/day and a BP maintained at less than 130/80 mmHg, with more than six-month therapy of ramipril, (5.7 +/- 0.4 mg/day, 13 +/- 2 month). The baseline data between the two groups showed no significantly differences. After a 12-week stabilization period (control period), 4 mg, once daily, dose of candesartan (combination period) followed by a placebo (placebo period), or vice versa, were administered in addition to the ramipril, for 12 weeks. The combination, with candesartan, did not change the Ccr, BP, serum and urinary electrolytes or the urea. The 24 hour urinary protein excretion rate was significantly reduced by the combination therapy in the patients with IgA nephropathy (3.1 +/- 0.3 g/day in combination, 4.2 +/- 0.3 in control, and 4.3 +/- 0.2 in placebo; p < 0.05). However, the patients with diabetic nephropathy showed no reduction in their proteinuria with the combination therapy (3.8 +/- 0.2 g/day in combination, 3.9 +/- 0.3 in control, and 4.1 +/- 0.3 in placebo; p=NS). The changes in proteinuria showed no relationship with the changes in the BP in IgA nephropathy. In conclusions, the benefit of combination therapy of its antiproteinuric effect was different between IgA and diabetic nephropathy over the 12-week trial. The difference in the pathophysiological role, and the importance of the renin- angiotensin system, between the two diseases might contribute to the discrepancy in the result. We suggest the discrimination of the underlying renal diseases in the study subjects is an important prerequisite for future studies on this issue.