Drug Induced Acute Renal Failure in Pregnancy- Management

Drug Induced Acute Renal Failure in Pregnancy

Acute renal failure is a most challenging clinical problem when it occurs in pregnancy. It requires an understanding of the normal physiology of the kidney in pregnancy and the natural history of different underlying renal diseases when pregnancy occurs.

                Acute renal failure defined as the condition in which the urine volume falls below 400 ml in 24 hours. Anuria is the absence of excretion of urine in 12 hours whereas oliguria is the term given to clinical condition.

                Because patients with chronic renal disease may present with worsening proteinuria, hypertension, and renal function, these disorders must be excluded from those conditions that cause acute deterioration of renal failure in otherwise normal women during pregnancy. As in all patients who develop acute renal failure, perennial, renal and post renal obstructive causes must be excluded.

Causes of Renal Failure

Drugs

·         Hemodynamic affects

·         Acute allergic interstitial nephritis

·         Direct toxicity to tubule

Pathogenesis

Reversible prerenal acute Renal Failure

Homodynamic disturbances can initially produce acute renal dysfunction that has the potential to be rapidly reversed, prompt recognition and treatment is important.

                Prolonged under perfusion of kidney may lead to failure of the compensatory mechanisms and hence a acute decline in GRR. The renal tubules are intact and become hyper functional: that is, tubular reabsortion of sodium and water is increased, partly through physical factors associated with changes in blood and urine flow and partly through influence of angiotensins, aldosterone and vasopressin. This leads to formation of low volume urine which is concentrated but low in sodium. These urinary changes may be absent in patients with impaired tubular function, e.g. pre-existing renal impairment, or those who have received loop diuretics.

Established Acute Renal Failure

Established ARF may develop following severe or prolonged under perfusion of kidney. In such cases, the histological pattern of acute tubular necrosis is usually seen. In patients without an obvious cause of prerenal ARF, alternative ‘renal’ and ‘post renal’ causes must be considered.

Ischemic tubular necrosis usually follows a period of shock, during which renal blood flow is greatly reduced. Even when systemic hemodynamic are restored, renal blood flow can remain as low as 20% of normal, due to swelling of endothelial cells of glomeruli and per tubular capillaries, and edema of the interstitium. Blood flow is further reduced by vasoconstrictors such as thromboxane, vasopressin, noradrenaline and angiotensin II, partly counterbalanced by release of intrarenal vasodilators prostaglandins. Thus in ischemic ATN there is reduced oxygen delivery to tubular cells. These cells are vulnerable to ischemia because they have high oxygen consumption in order to generate energy for solute reabsorption, particularly in thick ascending loop of henle.

The ischemic insult ultimately causes death of tubular cells, which may shed into the tubular lumen causing tubular obstruction. Focal breaks in the tubular basement membrane develop, allowing tubular contents to leak into the interstitial tissue and cause interstitial edema. In nephrotoxic ATN a similar sequence occours, but it is intitiated by direct toxicity of causative agent to tubular cells. Examples include aminoglycoside antibiotics such as gentamicin, cytotoxic agent cisplatin and the antifungal drug amphotericin B.

Clinical Presentation

The clinical presentation of both these conditions should be apparent, and appropriate diagnosis and treatment can then be promptly instituted. Renal cortical necrosis is another cause of renal failure that occurs more frequently in pregnancy and it must be differentiated from the many causes of acute tubular necrosis that may be associated with pregnancy. Those conditions that cause renal failure unique to pregnancy must always be considered when renal function deteriorates in the last trimester or the postpartum period. Severe pre-eclampsia, acute fatty liver of pregnancy and idiopathic postpartum acute renal failure may all present similar complications but the approach to each or these clinical disorders must be individualized. By understanding the causes of renal functional deterioration in pregnancy, a logical differential diagnosis can be established, allowing appropriate therapeutic decisions to preserve both maternal and fetal well-being.