John P. Hayslett

BACKGROUND: Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. METHODS: We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester. RESULTS: The mean (+/- SD) serum creatinine concentration increased from 1.9 +/- 0.8 mg per deciliter (168 +/- 71 mumol per liter) in early pregnancy to 2.5 +/- 1.3 mg per deciliter (221 +/- 115 mumol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent. Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency. Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent). The infant survival rate was 93 percent. CONCLUSIONS: Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high.

As the population of nephrons diminishes, while the dietary intake and/or endogenous production of water and solutes is unchanged, there is a proportional increase in the excretion of water and solute by individual residual nephrons. This adaptive change, which preserves zero net balance in the early phase of renal insufficiency, involves a reduction in the fractional reabsorption of substances derived from the initial glomerular ultrafiltrate and an increase in the rate of secretion of solutes that are extracted by tubular epithelial cells from peritubular blood. These compensatory changes are adequate to maintain electrolyte and water homeostasis until severe renal failure ensures (GFR less than 20% of normal). After a moderate reduction in nephron population there is no evidence that the factors that modulate ion transport are qualitatively different from those that regulate renal function in the intact subject, when the excretory load of solute is varied by changes in intake or endogenous production. In severe renal insufficiency, however, it seems likely that several factors, not present in the subject with intact renal function, also play an important role in modifying the excretion of water and electrolytes. For example, an osmotic diuresis in severe renal failure apparently decreases the tubular reabsorption of sodium and divalent cations and that of water. Moreover, elaboration of a partially identified "natriuretic" substance may participate in the regulation of electrolyte excretion in severe renal insufficiency. The appearance of these factors in severe renal insufficiency probably complements mechanisms that normally regulate the transfer of water and ions across tubular epithelium, since even after a marked reduction in GFR the urinary excretion of solutes and water changes proportionally with intake, although within narrower limits than exist in normal subjects. Studies in experimental animals and in man with acquired renal disease demonstrate the important role of other factors in compensatory adaptation, in addition to changes in tubular transport. The marked increases in glomerular filtration rate and nephron blood flow, which occur at least in some conditions, increase the absolute amount of water and solute delivered to the various nephron segments in ultrafiltrate and peritubular blood. Moreover, the expansion of extracellular fluid in severe renal failure inhibits tubular reabsorption of filtered water and solute in the same qualitative way that has been demonstrated in subjects with intact renal function. Quantitatively the response to acute volume expansion is exaggerated compared with control. Concomitant changes in renal hypertrophy and hyperplasia probably play an important role in functional adaptation. The apparent marked capacity for compensatory growth in all nephron segments and even in portions of tubular segments in parenchymal renal disease increases the area for transport by tubular epithelia in residual nephrons, as the overall number of nephrons diminishes...

The functional correlates of compensatory renal hypertrophy were studied by micropuncture techniques in rats after the removal of one kidney. The glomerular filtration rate increased to roughly the same extent in the whole kidney and in individual surface nephrons, resulting in a greater amount of sodium delivered to the tubules for reabsorption. The fraction of the glomerular filtrate absorbed [determined from the tubular fluid-to-plasma ratio (TF/P) for inulin] remained unchanged in both proximal and distal portions of the nephron. The way in which the tubules adjusted to nephrectomy, however, differed in proximal and distal convolutions. After nephrectomy, the reabsorptive half-time, indicated by the rate of shrinkage of a droplet of saline in a tubule blocked with oil, was unchanged in the proximal tubule but significantly shortened in the distal convoluted tubule. Nevertheless, steady-state concentrations of sodium in an isolated raffinose droplet in the distal as well as the proximal tubule were the same in hypertrophied kidneys as in control animals. Possible reasons for this paradox are discussed. Transit time through the proximal tubules was unchanged by compensatory hypertrophy, but transit time to the distal tubules was prolonged. Changes in renal structure resulting from compensatory hypertrophy were also found to differ in the proximal and the distal protions of the nephron. Although tubular volume increased in both protions, the volume increase was twice as great in the proximal tubule as in the distal. In order, therefore, for net reabsorption to increase in the distal tubule, where the changes in tubular volume are not so marked, an increase in reabsorptive capacity per unit length of tubule is required. This increase is reflected in the shortening of reabsorptive half-time in the oil-blocked distal tubule that was actually observed.