Prominent hyperplasia of renin-producing juxtaglomerular apparatus after chronic and complete blockade of the renin-angiotensin system in adult IgA nephropathy

Abstract

Juxtaglomerular apparatus (JGA) hyperplasia rarely happened in renal biopsy and has been controversial clinically, because synthesis and secretion of renin were susceptible to the effect of clinical condition and medication. Here we present the case of a 39-year-old who got JGA hyperplasia of IgA nephropathy (IgAN) after long-term inhibition of the renin-angiotensin system (RAS) with an angiotensin receptor blocker (ARB), and a direct renin inhibitor (DRI) in combination with a diuretic. He was diagnosed with IgAN in his first renal biopsy, and was treated with supra-maximal dosages of ARB, DRI and a diuretic. In the second biopsy, because of the massive proteinuria and occurrence of steroid-induced diabetes, it was revealed that the area and the number of JGA cells were strikingly increased in observed glomeruli. Immunohistopathologically, the both specimens were stained by human renin antibody. The hyperplastic JG cells contained a large amount of renin granules. Putative renin granules were observed in some interstitial cells adjacent to an afferent arteriole by electron microscopy. The increasing response of renin granules co-localized in prominent JGA hyperplasia should be worried while physicians treat hypertensive patients with potent RAS inhibitors and diuretics even though they have diabetes. This is the first report showing a clinical course of forming prominent JGA hyperplasia directly after a full combination of RAS inhibitors and diuretics in adult IgA nephropathy.

Keywords: IgA nephropathy; Juxtaglomerular apparatus; Renin-angiotensin system.

Fig. 1

Renal histopathology of the first biopsy. a Masson stain and b immunoperoxidase staining for IgA. c Immunoperoxidase staining for renin

Fig. 2

Renal histopathology of the second biopsy. a Masson stain, b immunoperoxidase staining for renin vesicles in the JGA and c the interstitium

Fig. 3

Electron microscopy. a Interstitial cells containing putative renin granules adjacent to tubular cells. b To observe putative renin granules well, a magnified picture of dotted box in a with scale bar (2.0 µm), and aa indicates afferent arteriole

Fig. 4

Clinical coarse around the first and second renal biopsy. R.Bx. renal biopsy, q./d. alternated-date, SBP systolic blood pressure, DBP diastolic blood pressure, BW body weight, Cr creatinine, U-P urinary proteinuria, U-OBR urinary occult blood reaction, U-RBC urinary red blood cell, hpf. high power field