Urolithiasis

Urolithiasis affects 0.03% of all pregnancies, a frequency similar to that of the general population. Colicky abdominal pain, recurrent UTI, and hematuria suggest urolithiasis. If the diagnosis is suspected, IV pyelogram (IVP) should be considered, which limits this study to the minimum number of exposures necessary to make the diagnosis. Ultrasound can also be used to establish the diagnosis without radiation exposure. However, ultrasound alone may be limited in securing a diagnosis of urolithiasis. In a recent multicenter, longitudinal study the authors noted, “Of the group treated surgically after imaging with ultrasound alone, 23% had no evidence of a ureteral stone, resulting in the lowest positive predictive value of the modalities used. Alternative imaging techniques, particularly low-dose computerized tomography, offer improved diagnostic information that can optimize management and avoid unnecessary intervention.” Newer ultrasound flow studies can actually follow flow from the ureter to the bladder, and they can detect obstruction without the use of ionizing radiation. If transabdominal ultrasound is limited, transvaginal ultrasound can also be used to visualize the distal ureter. Urine microscopy may detect crystals and can help distinguish the type of stone before it is passed. Serum calcium, phosphorous, and urate levels should be assayed for any woman with renal calculi to assist in the evaluation for possible hyperparathyroidism and gout.

Because of the physiologic hydroureter of pregnancy, 75% to 85% of women with symptomatic urolithiasis will spontaneously pass their stones. Treatment should therefore be conservative and should consist of hydration and narcotic analgesia. Epidural anesthesia has been advocated to establish a segmental block from T11 to L2, although it is unknown whether this promotes passage of the stone. Ureteral stenting to relieve obstruction is an option for managing pregnant women with renal stones. For refractory cases, nephrostomy tubes can also be used. It should be noted that pregnancy increases the risk of stent encrustation, which requires frequent stent exchange every 4 to 6 weeks until delivery. Lithotripsy is contraindicated during pregnancy.

Recurrent UTI with urease-containing organisms causes precipitation of calcium phosphate in the kidney that may lead to the development of staghorn calculi. Surgery is rarely indicated in women with this condition during gestation. Individuals with staghorn calculi should have frequent urine cultures, and bacteriuria should be treated aggressively. Recurrent infections pose a risk for chronic pyelonephritis with resultant loss of kidney function.

Glomerular Disease

Acute glomerulonephritis is an uncommon complication of pregnancy, with a reported incidence of 1 per 40,000 pregnancies. Poststreptococcal glomerulonephritis is rarely observed in the adult population. In this disorder, renal function tends to deteriorate during the acute phase of the disease but usually recovers in time. Acute glomerulonephritis can be difficult to distinguish from preeclampsia. Periorbital edema, a striking clinical feature of acute glomerulonephritis, is often seen in preeclampsia. However, hematuria, red blood cell (RBC) casts in the urine sediment, and depressed serum complement levels support the diagnosis of glomerulonephritis. A rise in antistreptolysin O titers may secure the diagnosis of poststreptococcal glomerulonephritis.

Treatment of acute glomerulonephritis in pregnancy is similar to that for the nonpregnant individual. Blood pressure control is essential, and careful attention to fluid balance is advised. Sodium intake should be restricted to 500 mg/day during the acute disease, and serum potassium levels must also be carefully monitored.

Packham and coworkers extensively reviewed 395 pregnancies in 238 women with primary glomerulonephritis. Remarkably, only 51% of the infants were born after 36 weeks’ gestation. Excluding therapeutic abortion, the fetal loss rate was 20%, with 15% occurring after 20 weeks’ gestation. IUGR was noted in 15% of the cases, and maternal renal function deteriorated in 15% of pregnancies and failed to resolve following delivery in 5% of the study population. Hypertension was recorded in 52% of the pregnancies and developed prior to 32 weeks’ gestation in 26%. In most cases, this blood pressure elevation was not an exacerbation of chronic hypertension. Eighteen percent of the women who developed de novo hypertension in pregnancy remained hypertensive postpartum, and increased proteinuria was recorded in 59% of these pregnancies and was irreversible in 15%. The highest incidence of fetal and maternal complications in women with glomerular disease occurred in those with primary focal and segmental hyalinosis and sclerosis, whereas the lowest incidence was observed in non–immunoglobulin A (IgA) diffuse mesangial proliferative glomerulonephritis . The presence of severe vessel lesions on renal biopsy was associated with a significantly higher rate of fetal loss after 20 weeks’ gestation. Packham and coworkers also studied 33 pregnancies in 24 patients with biopsy-proven membranous glomerulonephritis. Fetal loss occurred in 24% of pregnancies, preterm delivery was reported in 43%, and a term liveborn infant was delivered in only 33% of patients. Hypertension was noted in 46% of these pregnant women, and 30% had proteinuria in the nephrotic range during the first trimester. The presence of significant proteinuria during the first trimester correlated with poor fetal and maternal outcome.

Jungers and associates described 69 pregnancies in 34 patients with IgA glomerulonephritis. The fetal loss rate in this group was 15%. Preexisting hypertension was statistically associated with poor fetal outcome. Hypertension at the time of conception also correlated with a deterioration of maternal renal function during pregnancy. Hypertension in the first pregnancy was highly predictive of recurrence of hypertension in a subsequent pregnancy. Kincaid-Smith and Fairley analyzed 102 pregnancies in 65 women with IgA glomerulonephritis and noted that hypertension occurred in 63% of pregnancies, and it was severe in 18%. In this subset of women, a decline in renal function was observed in 22%. Abe reported 240 pregnancies in 166 women with preexisting glomerular disease and found that 8% of the pregnancies resulted in a spontaneous abortion, 6% in a stillbirth, and 86% in a liveborn infant. Most losses occurred in women with a GFR less than 70 mL/min and preexisting hypertension. Even though the majority of women with significant renal insufficiency had good pregnancy outcomes, the long-term prognosis for these cases was worse if the GFR was less than 50 mL/min and the serum creatinine was more than 1.5 mg/dL. The histopathogenic diagnosis of membranoproliferative glomerulonephritis seemed to carry the worst prognosis: 29% developed hypertension and 33% demonstrated a long-term decrease in renal function.

Imbasciati and Ponticelli summarized six studies that comprised a total of 906 pregnancies in 558 women with preexisting glomerular disease. The overall perinatal mortality was 13%. Hypertension, azotemia, and nephrotic-range proteinuria were the strongest predictive factors for a poor pregnancy outcome. In this report, the histologic type of glomerulonephritis had little correlation with pregnancy outcome. Hypertension persisted in 3% to 12% of patients who developed hypertension for the first time during pregnancy. In 25% of patients, hypertension worsened during pregnancy and normalized postpartum. Some of these cases represented superimposed preeclampsia. However, this diagnosis can be difficult to establish in women with baseline hypertension and proteinuria. Remarkably, only 3% of these 166 women experienced an acceleration of their glomerular disease after pregnancy.

Acute Renal Failure in Pregnancy

Acute renal failure (ARF) is defined as a urine output of less than 400 mL in 24 hours. To establish the diagnosis, ureteral and urethral obstruction must be excluded. The incidence of ARF during pregnancy is approximately 1 per 10,000. It is most frequently observed following sepsis or in cases of sudden severe volume depletion as a result of hemorrhage. ARF may also be observed with marked volume contraction associated with severe preeclampsia, dehydration from hyperemesis gravidarum, and with acute fatty liver of pregnancy.

The incidence of ARF in pregnancy has decreased over the years. Stratta and colleagues reported 81 cases of pregnancy-related ARF between 1958 and 1987, which accounted for 9% of the total number of ARF cases that required dialysis during that time. In three successive 10-year periods (1958–1967, 1968–1977, and 1978–1987), the incidence of pregnancy-related ARF fell from 43% to 2.8% of the total number of cases of ARF. The incidence declined from 1 in 3000 to 1 in 15,000 pregnancies over the study period. In these 81 cases of ARF, 11.6% experienced irreversible renal damage, the majority of which occurred in the setting of severe preeclampsia-eclampsia.

Renal ischemia is a common phenomenon in cases of ARF. With mild ischemia, quickly reversible prerenal failure results; with more prolonged ischemia, acute tubular necrosis occurs. This process is also reversible because glomeruli are not affected. Severe ischemia, however, may produce acute cortical necrosis. This pathology is irreversible, although on occasion, a small amount of renal function is preserved. Stratta and colleagues have reported 17 cases of ARF complicating pregnancies over 15 years, and all were observed in the setting of preeclampsia-eclampsia; cortical necrosis occurred in 29.5% of the cases, and progression of ARF to cortical necrosis did not appear to be related to maternal age, parity, gestational age, duration of preeclampsia prior to delivery, or eclamptic seizures. The only significant risk factor associated with cortical necrosis was placental abruption. In another study, Turney and coworkers demonstrated that acute cortical necrosis, which occurred in 12.7% of their patients with ARF, was associated with a 100% mortality within 6 years.

Sibai and colleagues studied the remote prognosis in 31 consecutive cases of ARF in patients with hypertensive disorders of pregnancy. Eighteen of the 31 patients had “pure” preeclampsia, whereas 13 pregnancies had other hypertensive disorders and renal disease; of the 18 patients with pure preeclampsia, 5% required dialysis during hospitalization, and all 18 patients had acute tubular necrosis. Of the other 13 women, 42% required dialysis, and three patients had bilateral cortical necrosis. The majority of pregnancies in both groups were complicated by placental abruption and hemorrhage. All 16 surviving patients in the pure preeclampsia group recovered normal renal function on long-term follow-up. Conversely, 9 of the 11 surviving patients in the nonpreeclamptic group required long-term dialysis, and four ultimately died of end-stage renal disease. In a follow-up study, Turney and colleagues found that maternal survival was adversely affected by increasing age. Their 1-year maternal survival rate was 78.6%, and follow-up of survivors showed normal renal function up to 31 years after ARF.

Individuals with reversible ARF experience a period of oliguria of variable duration followed by polyuria, or a high-output phase. It is important to recognize that BUN and serum creatinine levels continue to rise early in the polyuric phase. During the recovery phase, urine output approaches normal. In these patients, it is important to monitor electrolytes frequently and to carefully treat any imbalance. The urine to plasma osmolality ratio should be determined early in the course of the disease. If the ratio is 1.5 or greater, prerenal pathology is likely, and the disorder tends to be of shorter duration and of less severity. A ratio near 1.0 suggests acute tubular necrosis.

The main goal of treatment is the elimination of the underlying cause. Volume and electrolyte balance must be evaluated frequently. To assess volume requirements, invasive hemodynamic monitoring may be useful. This is especially true during the polyuric phase. Central hyperalimentation may also be required if renal failure is prolonged.

Acidosis frequently occurs in cases of ARF. Therefore, arterial blood gases should be followed regularly. Acidosis must be treated promptly because it can exacerbate hyperkalemia, which can be fatal. If hyperkalemia develops, potassium restriction should be instituted immediately. Sodium bicarbonate, used to treat acidosis, may overload the patient with sodium and water. In such cases, peritoneal dialysis or hemodialysis may be necessary. The main indications for dialysis in ARF of pregnancy are hypernatremia, hyperkalemia, severe acidosis, volume overload, and worsening uremia.

Hemolytic Uremic Syndrome

The hemolytic uremic syndrome (HUS) is a rare idiopathic disorder that must be considered when a patient exhibits signs of hemolysis and decreasing renal function, par­ticularly during the third trimester and in the postpartum period. This idiopathic syndrome may occur as early as the first trimester and as late as 2 months postpartum, and it is part of a spectrum of disease that may also include thrombotic thrombocytopenic purpura (TTP; see Chapter 44 ). Most individuals have no predisposing factors. Prodromal symptoms include vomiting, diarrhea, and a flulike illness. A review of 49 cases documented a 61% mortality rate, although with improved intensive care monitoring and treatment, the prognosis is now much improved.

Disseminated intravascular coagulation (DIC) with hemolysis usually accompanies HUS. However, DIC is not the cause of the syndrome. Microscopically, the kidney shows thrombotic microangiopathy. The glomerular capillary wall is thick, and biopsy specimens taken later in the course of the disease show severe nephrosclerosis and deposition of the third component of complement (C ₃ ).

Some investigators believe that this syndrome is due to decreased renal production of prostacyclin, infusions of which have been used to treat these patients, although such therapy remains experimental. One observer noted a decrease in antithrombin III in a woman with postpartum HUS. This patient was successfully treated with an infusion of antithrombin III concentrate.

Coratelli and coworkers reported a case of HUS diagnosed at 13 weeks’ gestation and confirmed by renal biopsy. Circulating endotoxin was detected and was progressively reduced by hemodialysis performed daily from the third to the ninth day of the disease. Complete normalization of renal function occurred by day 34. These investigators propose that initiation of early dialysis may play an important role in supporting patients through the disease process. They also propose that endotoxins are key pathogenic factors in the disorder. In contrast, Li and coworkers failed to measure any endotoxin in a patient’s serum who developed HUS after an uncomplicated cesarean delivery; this patient eventually underwent dialysis and recovered. Plasma exchange in cases of ARF caused by postpartum HUS can be vital to the treatment of this condition.

Polycystic Kidney Disease

Adult polycystic kidney disease is an autosomal-dominant disorder that usually begins to manifest during the fifth decade of life. Reproductive-age women may occasionally display symptoms, and hypertension is a key component of this disorder. If a woman with adult polycystic kidney disease becomes pregnant, hypertension may be greatly exacerbated and may not improve following delivery. However, the overall prognosis for the disorder does not appear to worsen with an increasing number of pregnancies.

Vesicoureteral Reflux

Although vesicoureteral reflux may be exacerbated with pregnancy, it usually does not result in morbidity unless reflux becomes severe. If reflux is significant enough to warrant surgery, this should ideally be undertaken prior to pregnancy. Even with surgical correction, women with ureterovesical reflux remain at increased risk for pyelonephritis and should have urine cultures performed frequently. If indicated prior to pregnancy, antibiotic suppression should be continued.

Brandes and Fritsche have reported a case of ARF that resulted from ureteral obstruction by a gravid uterus. This case was complicated by a twin gestation with polyhydramnios at 34 weeks’ gestation. The serum creatinine level peaked at 12.2 mg/dL but resolved immediately after amniotomy. In cases remote from term, ureteral stenting or dialysis may be necessary if significant obstruction and/or reflux is present.

Renal Artery Stenosis

Renal artery stenosis is rarely discovered during pregnancy. This disorder may present as chronic hypertension with superimposed preeclampsia or as recurrent isolated preeclampsia. Although Doppler flow studies may be suggestive, renal angiography is the most specific and sensitive diagnostic test. Percutaneous transluminal angioplasty can be carried out at the time of angiography.

Nephrotic Syndrome

The nephrotic syndrome was initially described as a 24-hour urine protein excretion equal to or in excess of 3.5 g, reduced serum albumin, edema, and hyperlipidemia. Currently, the syndrome is defined by proteinuria alone, which is often the result of glomerular damage. The most common etiology of nephrotic syndrome in pregnancy, especially in the third trimester, is preeclampsia. Other etiologies include membranous and membranoproliferative glomerulopathy, minimal change glomerulopathy, lupus nephropathy, hereditary nephritis, diabetic nephropathy, renal vein thrombosis, and amyloidosis.

Women with a newly diagnosed or persistent nephrotic syndrome need close monitoring during pregnancy. Whenever possible, the etiology of the proteinuria should be determined. In some cases, steroid therapy may be used to treat this condition; however, depending on the etiology, its use can actually aggravate the underlying disease process. One common complication of nephrotic syndrome in pregnancy is profound edema secondary to protein excretion, which is further complicated by the normal decline in serum albumin associated with pregnancy. Another complication is the development of a hypercoagulable state precipitated by urinary losses of antithrombin III, reduced levels of proteins C and S, hyperfibrinogenemia, and enhanced platelet aggregation. For this reason, prophylactic anticoagulation may be considered for affected pregnant women.