Comparison in renal histology between Japanese obese and non-obese microalbuminuric type 2 diabetic patients

Masao Kanauchi

First Department of Internal Medicine Nara Medical University Nara Japan Email: kanauchi{at}nmu-gw.naramed-u.ac.jp

Sir,

Although obesity is considered to be a cause of albuminuria and several studies have indicated a significant correlation between urinary albumin excretion and increasing body mass index (BMI) in both non-diabetic [1,2] and diabetic subjects [3], the majority of these studies were reported in Caucasians. Only limited data exist for Japanese subjects, probably because Japanese people are relatively lean. Furthermore, there is very little information about the association between obesity-related albuminuria and renal histology. The aim of this study was to determine a possible association between obesity and albuminuria analysed by renal biopsy in Japanese subjects with incipient diabetic nephropathy.

We studied 49 type 2 diabetic patients who had undergone renal biopsy at Nara Medical University Hospital. Inclusion criteria were age 75 years or less, serum creatinine concentration <2.0 mg/dl and persistent microalbuminuria (defined as an albumin excretion rate of between 30 and 300 mg/day). Obesity was defined as a BMI >25 kg/m2, because Japanese subjects are relatively lean. Creatinine clearance (Ccr) was defined using 24 h urine. Tissue specimens obtained by renal biopsy were processed for evaluation using light microscopy. The severity of both diffuse and nodular changes was graded from 0+ to 4+ using Gellman's criteria [4]. The severity of arteriolar changes was graded from 0+ to 3+ using Takazakura's criteria [5]. The severity of tubulointerstitial lesions was determined by a semi-quantitative estimate of the space occupied by fibrous tissue and/or interstitial infiltrates as follows: 0+ (normal); 1+ (damaged area <10%); 2+ (10% <damaged area <30%); and 3+ (30% <damaged area). The total injury score was the sum of the above 4 scores. No patient showed evidence of other types of primary renal disease superimposed on diabetic nephropathy.

No difference between obese (n=17) and non-obese (n=32) patient groups was found for mean age, systolic and diastolic blood pressure, HbA1c or urinary albumin excretion rate (Table 1Go). The known duration of diabetes was significantly shorter in the obese group than in the non-obese group. Adjusted Ccr per 1.73 m2 BSA was significantly higher in obese group than in non-obese group. There were no significant differences in the diffuse, nodular or tubulointerstitial scores between the two groups, but the arteriolar score was significantly higher in non-obese group than in obese group. The total injury score showed a trend toward higher values in the non-obese group, but the difference did not reach the level of statistical significance (P=0.08).


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Table 1.  Patients characteristics and renal scores

 
We found a significantly shorter duration of diabetes and a significantly higher Ccr in obese microalbuminuric subjects than in their non-obese counterparts. One explanation for albuminuria complicating obesity is the increase in glomerular filtration rate [6]. Haemodynamic modifications such as increased fluid volume, cardiac output and renal blood flow may contribute to glomerular hyperfiltration. However, increased sodium reabsorption in the renal tubule has been reported in obesity [7]. Sustained elevations in glomerular capillary pressure are found in obese animal model [8]. One limitation of our study is that plasma insulin levels were not available in our subjects. Hyperinsulinaemia secondary to insulin resistance could be involved in the increase in urinary albumin excretion since insulin has renal haemodynamic effects. Hyperinsulinaemia induces renal vasodilation, increased plasma flow and increased glomerular hydrostatic pressure [9]. Yet, it is not clear whether hyperinsulinaemia alone causes increased albuminuria. High protein intake and genetic susceptibility may confound the independent effects of hyperinsulinaemia on albuminuria. These variables were not evaluated in the present study.

In summary, in Japanese microalbuminuric type 2 diabetic patients with mild renal failure, renal lesions are similar in patients with and without obesity. The longitudinal studies are important for further investigation.

References

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  2. Valensi P, Assayag M, Busby M, Paries J, Lormeau B, Attali J-R. Microalbuminuria in obese patients with or without hypertension. Int J Obesity 1996; 20:574–579[ISI]
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  4. Gellman DD, Pirani CL, Soothill JF, Muehrcke RC, Kark RM. Diabetic nephropathy; a clinical and pathologic study based on renal biopsies. Medicine 1959; 38:312–367
  5. Takazakura E, Nakamoto Y, Hayakawa H et al. Onset and progression of diabetic glomerulosclerosis. Diabetes 1975; 24:1–9[Abstract]
  6. Wesson DE, Kurtzman NA, Frommer JP. Massive obesity and nephrotic proteinuria with a normal renal biopsy. Nephron 1985; 40:235–237[ISI][Medline]
  7. Hall JE. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens 1997; 10:S49–S55[ISI]
  8. O'Donnell MP, Kasiske BL, Cleary MP, Keane WF. Effects of genetic obesity on renal structure and function in the Zucker rat. J Lab Clin Med 1985; 106:605–610[ISI][Medline]
  9. Nelson S, Jensen MD. Relationship between urinary albumin excretion, body composition, and hyperinsulinemia in normotensive glucose-tolerant adults. Diabetes Care 1999; 22:1728–1733[Abstract]




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