Abstract
BackgroundThe total number of nephrons has been measured mainly from post-mortem studies and only in selected populations. Data from living subjects are scanty, and direct comparisons among different glomerular diseases are lacking. The present work exploits modern methodology to estimate the total nephron number in glomerulopathies with prevalent proteinuria/nephrotic syndrome versus glomerulopathies with nephritic syndrome (IgA nephropathy (IgAN), lupus nephritis), thus extending previous observations about the number and function of glomeruli in different physiological and pathological states.MethodsThis is a retrospective study based on one hundred and seven patients who have undergone renal biopsy. The glomerular density has been estimated from the biopsy specimens and the total cortical volume has been obtained from ultrasound recordings. Stereological methods have been applied to calculate the total number of nephrons and their volume. The correlation between clinical parameters and quantitative morphological data have studied using the Pearson correlation coefficient (r).ResultsThe total number of nephrons inversely correlated with the systolic blood pressure (r = −0.4, p < 0.05). In proteinuric diseases, such as focal segmental glomerulo-sclerosis (FSGS), membranous nephropathy (MN) and diabetes, the change in estimated GFR (eGFR) directly correlated with the total number of non-sclerotic glomeruli (NSG) (r = 0.62, p < 0.01), whereas in nephritic syndrome no significant correlation was observed. The alterations in eGFR occurring in nephritic syndromes such as IgAN cannot be explained on the basis of the number of NSG.DiscussionThe fusion of the podocyte foot-processes that typically occurs in purely proteinuric diseases does not modify the glomerular filtration rate: therefore in these situations, the change in eGFR depends mainly on the number of available glomeruli. On the other side, the eGFR decrease occurring in nephritic syndromes, such as IgAN, cannot be explained simply on the basis of the number of NSG and likely depends on the substantial involvement of the mesangial axis. Future studies should verify whether these changes are reversible with appropriate therapy, thus reversing eGFR decrease.
Highlights
According to the “intact nephron hypothesis” proposed by Neal Bricker in 1960, a greater fraction of the total renal excretion must be performed by fewer, functionally intact tubules when kidney damage occurs (Bricker, Morrin & Kime, 1960; Hayman et al, 1939; Platt, 1952)
The alterations in estimated GFR (eGFR) occurring in nephritic syndromes such as IgA nephropathy (IgAN) cannot be explained on the basis of the number of non-sclerotic glomeruli (NSG)
When all data were pooled, the total number of nephrons inversely correlated with the systolic (SBP) blood pressure (SBP: r = −0.40, p = 0.02; diastolic blood pressure (DBP): r = −0.35, p = 0.06)
Summary
According to the “intact nephron hypothesis” proposed by Neal Bricker in 1960, a greater fraction of the total renal excretion must be performed by fewer, functionally intact tubules when kidney damage occurs (Bricker, Morrin & Kime, 1960; Hayman et al, 1939; Platt, 1952). In autopsy studies, a correlation between the total number of glomeruli and mean glomerular volume has been repeatedly observed (Hoy et al, 2003; Hughson et al, 2008), suggesting that a lower number of nephrons is compensated by glomerular hypertrophy. Results: The total number of nephrons inversely correlated with the systolic blood pressure (r = −0.4, p < 0.05) In proteinuric diseases, such as focal segmental glomerulo-sclerosis (FSGS), membranous nephropathy (MN) and diabetes, the change in estimated GFR (eGFR) directly correlated with the total number of non-sclerotic glomeruli (NSG) (r = 0.62, p < 0.01), whereas in nephritic syndrome no significant correlation was observed. Discussion: The fusion of the podocyte foot-processes that typically occurs in purely proteinuric diseases does not modify the glomerular filtration rate: in these situations, the change in eGFR depends mainly on the number of available glomeruli.
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