Morphology of diabetic glomerulopathy and relationship to hypertension

The mutual relationship between elevated blood pressure and structural changes in the kidney is still an area with more open questions than clear answers. Indirect evidence is available concerning one aspect: When hypertension is present it has a significant impact on the further progression of the structural changes. This evidence is available only in terms of the effect of antihypertensive treatment on the preservation of renal function. Since it has been shown that the demise in renal function in long-term diabetics is closely related to the development of advanced diabetic glomerulopathy, it seems likely that normalization of the blood pressure leads to a slowing of this development. Structural studies to elucidate these interactions are, however, not available. An intriguing question is whether the relationship is interactive also in the other direction. Focusing on the alterations within the glomeruli, the fact is that the glomerulopathy develops over several years before it comes to the stage when clinical signs appear. Thus, diabetics with 'incipient nephropathy' clearly demonstrate basement membrane (BM) accumulation, showing as increased BM-thickness and increase in mesangial matrix volume. Since this is the most likely point of time for hypertension to develop the necessary condition obtains, that the development of hypertension might be triggered by structural abnormalities in the kidney. The mechanisms of action at this point of time remain speculative. The relationship between structural parameters characterizing diabetic glomerulopathy and the blood pressure level was studied in a series of 14 IDDM patients, representing a span of renal functional impairment. Mean blood pressure in the group was 117 mmHg, with a range from 87-122 mmHg. None of the patients received antihypertensive treatment at the time of biopsy. The blood pressure level did not correlate with the parameters of diabetic glomerulopathy (BM-thickness, volume fraction of mesangium and volume fraction of mesangial matrix), nor with the percentage of occluded glomeruli or the estimate of filtration surface per nephron. The results of this study, therefore, did not provide evidence that either of these structural changes is directly responsible for the induction of hypertension. Hypertension in diabetics could still be related to renal structural changes, to be found outside the glomeruli; perphaps glomerular changes in combination with other abnormalities might be involved in the pathogenesis. The diabetic kidney in these stages demonstrates a variety of pathological changes, to mention arterio- and arteriolosclerosis, and increase in the interstitium. A likely suspect is the juxtaglomerular arterioles, which to date have not been studied in detail in diabetic patients. We propose as a working hypothesis that the rising blood pressure is triggered by decreasing filtration surface in individual subjects, if other compensatory mechanisms are not possible, or when they have been exhausted. The development of hypertension in diabetics is therefore a sign of critical conditions in the kidney, which - unless intervention takes effect - will progress to end stage renal failure.