Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.

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In a prospective study of idiopathic glomerulonephritis we determined the natural history of 49 adult patients (12 primary IgA nephropathy, 13 thin GBM nephropathy, 20 normal renal tissue and 4 miscellaneous nephropathies) who presented with idiopathic non-proteinuric non-azotemic hematuria of at least six months duration, in the absence of hypertension and with a negative urological work-up. The median follow-up was 11 years with a range of 8 to 14 years. At the end of the follow-up, renal function had remained stable in all subsets except for those with miscellaneous disease. Hematuria was still present in all patients with thin GBM nephropathy, in all but two patients with IgA nephropathy who went into immunopathological remission, in three out of four miscellaneous nephropathies, and in seven out of 20 patients with normal renal tissue. Of the latter patients five had a history suggestive of urolithiasis at follow-up, which was in the absence of hypercalciuria and hyperuricosuria. Seven thin GBM patients, five IgA nephropathy patients and three miscellaneous nephropathies developed hypertension; the incidence of hypertension in each subset was significantly higher than in patients with normal renal tissue. This study shows that in young adults with idiopathic chronic non-proteinuric hematuria of four years duration, renal biopsy will give a definite diagnosis in 86% of the patients, and that those patients with so-called minor glomerular diseases are at high risk for hypertension. Those patients with normal renal tissue have a high incidence of urolithiasis and should have a urological follow-up.

A large fraction of the skin-homing T-cell population resides in the skin even under resting, non-inflammatory conditions. Here, we used a crawl-out culture method to retrieve T cells from human skin and characterized them using flow cytometric analysis. On average, 48000 viable, non-proliferating cells were retrieved per biopsy. We found that human skin contains a larger fraction of IL-17-, IL-4-, IL-10-and IL-22-positive T cells as compared with paired blood samples. Our research indicates that it is feasible to use the crawl-out method in combination with flow cytometry to characterize T-cell subpopulations in patient-derived skin biopsies. This method enables further study of the skin immune system and could function as a valuable tool for evaluation of the effects of immunotherapy in skin diseases.

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