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Intact Nephron Hypothesis (INH) was first postulated by Bricker et al.

in January 1960
issue of The American Journal of Medicine. The hypothesis is based on the assumption that
the many different forms of chronic renal disease give rise to the same pattern of chemical
and functional derangements relating to nephron destruction. Further, it suggests that the
functional capacity of the residual nephrons of the diseased kidney is largely independent of
the specific form of renal disease. So, they considered the concepts of pathologic physiology
without reference to the underlying renal disease throughout their discussion.
Generally, it is considered that in chronic renal disease the progressively decreasing number
of nephrons is responsible for many of the abnormalities that develops while homeostasis is
maintained by the persisting nephrons, enabling the patient to survive. To overcome the
increasing demands on the residual nephrons to maintain balance of solute and fluid in the
body, the function of each nephron must be enhanced. For substances which are excreted
predominantly by filtration and do not depend upon active tubular transport processes,
increased plasma levels alone will account in large part for the normal excretion rates.
However, for substances which are handled by active tubular transport mechanisms, normal
excretion by a decreased number of nephrons demands a high degree of functional efficiency.
The authors proposed that the diseased kidney functions in an orderly and predictable
manner. They designed an experiment with dogs where renal lesion was induced in a single
kidney and the other kidney was maintained intact. Two separate and permanent urinary
bladders were surgically formed allowing simultaneous and serial studies. Authors presented
and discussed following points based on their experimental data as well as references:
1. The glomerulo-tubular balance is maintained in diseased kidney.
2. The urine concentrating and diluting capacity of kidneys were intact in diseased
kidneys.
3. The diseased kidney can make adaptive changes to excretion of sodium (as well as
chloride) during state of sodium deprivation and natruresis.
4. The pattern of potassium excretion, phosphate reabsorption, glucose reabsorption and
amino acid by diseased kidney are comparable to those simultaneously observed in
the intact organ.
5. The diseased kidney is capable to stabilize pH when acidosis occurs.
Based on these observations and supporting clinical and experimental references, authors
suggested that the majority of surviving nephrons in the patient with bilateral renal disease
similarly are functionally intact. They concluded that the diseased kidney has reduced
population of nephrons and majority of them maintain normal functional capabilities. They
also stated that the abnormalities observed in function in bilateral renal disease may relate to
adaptive changes caused due to the reduced number of nephrons and the abnormalities in the
body fluids instead of structural changes in nephrons. The overall flexibility of the diseased
kidney is reduced as the number of remaining nephron decreases but the pattern of excretion
of all substances is orderly and predictable.
In editorial that they published in 1969, they revised their hypothesis. They restated that the
majority of the active nephrons in chronic renal disease function normally. When there is
functional deficiency in glomerular or tubular process in a nephron due to structural damage,
there is simultaneous and proportional changes in other functional systems in the same
nephrons. Moreover, there is relative homogeneity of golmerulo-tubular balance among the
surviving nephrons and there is continuing adaptive changes as the kidney disease advances.
In essence, INH is a pathologic physiological analysis of chronically diseased kidney which
states that diseased kidney regulates its function in response to the needs of the organism by
making adaptive functional changes.