Renal diseases in pregnancy

Renal diseases in pregnancy

Renal and urinary tract disorders are commonly encountered in pregnancy. Some precede pregnancy—one example nephrolithiasis. In some women, pregnancy-induced changes may predispose to development or worsening of urinary tract disorders—an example is the markedly increased risk of pyelonephritis. Finally, there may be complications unique to pregnancy such as preeclampsia. With good prenatal care, most women with these disorders will likely develop no long-term serious consequences.
Pregnancy-Induced Urinary Tract Changes
A remarkable number of changes are observed in the urinary system as a result of pregnancy . Kidney size increases slightly. The glomerular filtration rate (GFR) and renal plasma flow increase early in pregnancy. The GFR increases as much as 25 percent by the second week after conception and 50 percent by the beginning of the second trimester. Renal plasma flow increases , so elevated glomerular filtration persists until term, even though renal plasma flow decreases during late pregnancy but remain 50% greater than pre pregnancy levels. Primarily as a consequence of this elevated GFR, approximately 60 percent of women report urinary frequency during pregnancy.80% develop edema due to physiological retention of Na
Renal Changes in Normal Pregnancy

Alteration

Clinical Relevance
Kidney size
Approximately 1 cm longer on radiograph
Size returns to normal postpartum
Dilatation
Resembles hydronephrosis on sonogram or IVP (more marked on right)
Can be confused with obstructive uropathy; retained urine leads to collection errors; renal infections are more virulent; may be responsible for "distension syndrome"; elective pyelography should be deferred to at least 12 weeks postpartum
Renal function
Glomerular filtration rate and renal plasma flow increase ~50%
Serum creatinine decreases during normal gestation (creatinine clearance rise by 50%); >0.8 mg/dL (>72 mol/L) creatinine already borderline; protein (up to 300 mg per 24 hours), amino acid, and glucose excretion all increase
Maintenance of acid-base
Decreased bicarbonate threshold; progesterone stimulates respiratory center
Serum bicarbonate decreased by 4–5 mEq/L; PCO2 decreased 10 mm Hg; a PCO2 of 40 mm Hg already represents CO2 retention
Plasma osmolality
Osmoregulation altered: osmotic thresholds for AVP release and thirst decrease; hormonal disposal rates increase
Serum osmolality decreases 10 mOsm/L (serum Na ~5 mEq/L) during normal gestation; increased placental metabolism of AVP may cause transient diabetes insipidus during pregnancy


Orthostatic Proteinuria
Orthostatic or postural proteinuria has been observed in up to 5 percent of normal young adults. Without other evidence of renal disease, the pregnant woman with orthostatic proteinuria should be evaluated for bacteriuria, abnormal urinary sediment, reduced glomerular filtration, and hypertension. In the absence of these, orthostatic proteinuria is probably inconsequential.
Urinary Tract Infections
These are the most common bacterial infections during pregnancy. Although asymptomatic bacteriuria is the most common, symptomatic infection includes cystitis, or it may involve the renal calyces, pelvis, and parenchyma—pyelonephritis.
Organisms that cause urinary infections are those from the normal perineal flora. Approximately 90 percent of Escherichia coli strains that cause nonobstructive pyelonephritis. Although pregnancy itself does not enhance these virulence factors, urinary stasis and vesicoureteral reflux predispose to symptomatic upper urinary infections. Diabetics are especially susceptible to developing pyelonephritis.
Asymptomatic Bacteriuria
This refers to persistent, actively multiplying bacteria within the urinary tract in asymptomatic women. Its prevalence in nonpregnant women is 5 to 6 percent and depends on parity, race, and socioeconomic status.
The highest incidence is in African-American multiparas with sickle-cell trait, and the lowest incidence is in affluent white women of low parity. Because most women have recurrent or persistent bacteriuria, it frequently is discovered during prenatal care. The incidence during pregnancy is similar to that in nonpregnant women and varies from 2 to 7 percent.
Bacteriuria is typically present at the time of the first prenatal visit, and if an initial positive urine culture is treated, fewer than 1 percent of women develop urinary infection.
A clean-voided specimen(MSU) containing more than 100,000 organisms per milliliter is diagnostic. It may be prudent to treat when lower concentrations are identified, because pyelonephritis develops in some women with colony counts of 20,000 to 50,000 organisms/mL.
70-90% due to E.coli derived from large bowel
Colonization of UT results from ascending infection from the perineum and is related to sexual intercourse
Significance
If asymptomatic bacteriuria is not treated, approximately 25 percent of infected women will develop symptomatic infection during pregnancy. Eradication of bacteriuria with antimicrobial agents prevents most of these . In some, but not all studies, covert bacteriuria has been associated with preterm or low-birth weight infants, preterm delivery, pregnancy-associated hypertension, and anemia.
Bacteriuria that persists or recurs after delivery has been associated with pyelographic evidence of chronic infection, obstructive lesions, and congenital abnormalities.
Treatment
Bacteriuria responds to empirical treatment with any of several antimicrobial regimens . Although selection can be based on in vitro susceptibilities, in our extensive experience, empirical oral treatment for 10 days with nitrofurantoin macrocrystals, 100 mg at bedtime, is usually effective
Oral Antimicrobial Agents Used for Treatment of Pregnant Women with Asymptomatic Bacteriuria

Single-dose treatment

Amoxicillin 3 g
Ampicillin 2 g
Cephalosporin 2 g
Nitrofurantoin 200 mg
Trimethoprim-sulfamethoxazole 320/1600 mg
3-day course
Amoxicillin 500 mg three times daily
Ampicillin 250 mg four times daily
Cephalosporin 250 mg four times daily
Ciprofloxacin 250 mg twice daily
Levofloxacin 250 mg daily
Nitrofurantoin 50 to 100 mg four times daily; 100 mg twice daily
Trimethoprim-sulfamethoxazole 160/800 mg two times daily
Other
Nitrofurantoin 100 mg four times daily for 10 days
Nirofurantoin 100 mg twice daily fo 7 days
Nitrofurantoin 100 mg at bedtime for 10 days
Treatment failures
Nitrofurantoin 100 mg four times daily for 21 days
Suppression for bacterial persistence or recurrence
Nitrofurantoin 100 mg at bedtime for remainder of pregnancy


Cystitis and Urethritis
Lower urinary infection during pregnancy may develop without antecedent covert bacteriuria. Cystitis is characterized by dysuria, urgency, and frequency, but with few associated systemic findings. Pyuria and bacteriuria are usually found. Microscopic hematuria is common, and occasionally there is gross hematuria from hemorrhagic cystitis .
Although cystitis is usually uncomplicated, the upper urinary tract may become involved by ascending infection. Almost 40 percent of pregnant women with acute pyelonephritis have preceding symptoms of lower tract infection.
Treatment
Women with cystitis respond readily to any of several regimens. Most of the three-day regimens listed in table above are usually 90-percent effective.
Lower urinary tract symptoms with pyuria accompanied by a sterile urine culture may be from urethritis caused by Chlamydia trachomatis.
Several non pharmacological maneuvers may help to prevent recurrence which include( increased water intake and emptying bladder after intercourse)
Mucopurulent cervicitis usually coexists, and erythromycin therapy is effective.
Acute Pyelonephritis
Renal infection is the most common serious medical complication of pregnancy.
Clinical Findings
Renal infection develops more frequently in the second trimester, and nulliparity and young age are associated risk factors . It is unilateral and right-sided in more than half of cases, and it is bilateral in a fourth. There is usually a rather abrupt onset with fever, shaking chills, and aching pain in one or both lumbar regions. Anorexia, nausea, and vomiting may worsen dehydration. Tenderness usually can be elicited by percussion in one or both costovertebral angles. The urinary sediment contains many leukocytes, frequently in clumps, and numerous bacteria. Bacteremia is demonstrated in 15 to 20 percent of these women. E. coli is isolated from urine or blood in 70 to 80 percent of infections, Klebsiella pneumoniae in 3 to 5 percent, Enterobacter or Proteus in 3 to 5 percent, and gram-positive organisms including group B Streptococcus in up to 10 percent of cases.
The differential diagnosis includes, among others, labor, chorioamnionitis, appendicitis, placental abruption, or infarcted leiomyoma,pneumonia, cholecystitis, biliary colic ,degenerated fibroid, gastroenteritis . Evidence of the sepsis syndrome is common.
Plasma creatinine is monitored because early studies reported that 20 percent of pregnant women developed renal dysfunction.
RF include steroid therapy* polycystic kidneys* congenital abnormalities of renal tract* urinary tract calculi and DM
Management
One scheme for management of acute pyelonephritis is shown in Table below. Intravenous hydration to ensure adequate urinary output is the cornerstone of treatment. Antimicrobials are also begun promptly, however, their administration may initially worsen endotoxemia from bacterial lysis. Ongoing surveillance for worsening of sepsis syndrome is monitored by serial determinations of urinary output, blood pressure, pulse, and temperature. High fever should be lowered with a cooling blanket or acetaminophen. This is especially important in early pregnancy because of possible teratogenic effects of hyperthermia
Management of the Pregnant Woman with Acute Pyelonephritis

Hospitalize patient

Obtain urine and blood cultures
Evaluate hemogram, serum creatinine, and electrolytes
Monitor vital signs frequently, including urinary output—consider indwelling catheter
Establish urinary output to >50 mL/hr with intravenous crystalloid
Administer intravenous antimicrobial therapy
Obtain chest radiograph if there is dyspnea or tachypnea
Repeat hematology and chemistry studies in 48 hours
Change to oral antimicrobials when afebrile
Discharge when afebrile 24 hours, consider antimicrobial therapy for 7 to 10 days
Repeat urine culture 1 to 2 weeks after antimicrobial therapy completed


Antimicrobial therapy usually is empirical, and ampicillin plus gentamicin; cefazolin or ceftriaxone
Management of Nonresponders
If there is no clinical improvement by 48 to 72 hours, then sonography is recommended to look for urinary tract obstruction manifest by abnormal ureteral or pyelocaliceal dilatation.
Although most women with continuing infection have no evidence of obstruction, some are found to have calculi. Even though renal sonography will detect hydronephrosis, stones are not always visualized in pregnancy. If stones are strongly suspected despite a nondiagnostic sonographic examination, a plain abdominal radiograph will identify nearly 90 percent. Other causes of persistent infection are an intrarenal or perinephric abscess . Obstruction can be relieved by cystoscopic placement of a double-J ureteral stent. Because these stents tend to become encrusted, we have found percutaneous nephrostomy to be a better option as the stents are easier to replace. Surgical removal of stones may be required in some cases.

Follow-Up

Recurrent infection—either covert or symptomatic—is common and develops in 30 to 40 percent of women following completion of treatment for pyelonephritis. Unless other measures are taken to ensure urine sterility, nitrofurantoin, 100 mg orally at bedtime, is given for the remainder of the pregnancy.
Chronic Renal Disease
Chronic renal disease is a pathophysiological process that ultimately results in end-stage renal disease (ESRD) through a progressive loss of nephron number and function. It can be caused by multiple etiologies and must be present for at least 3 months to be considered chronic. the most common causes of ESRD are diabetes—33 percent, hypertension—24 percent, glomerulonephritis—17 percent, and polycystic kidney disease—15 percent.
In most young women with these diseases, there is usually some renal insufficiency, proteinuria, or both. For counseling regarding fertility and pregnancy outcome, it is important to determine the degree of renal functional impairment and associated hypertension. Successful pregnancy outcome in general may be more related to these two factors than to the specific underlying disorder.
Effects of pregnancy the risks include
*accelerated decline in renal function
*rising HTN
*worsening proteinuria
Effect of CRD on pregnancy
Risks include
*miscarriage
*PE
*IUGR
*preterm delivery
*fetal death
Factors influencing outcome
*presence and degree of renal impairment
*presence and degree of proteinuria
*the underlying type of chronic renal disease
A general prognosis can be estimated by considering women in arbitrary categories of renal function. These include normal or mild impairment, defined as a serum creatinine of less than 1.5 mg/dL(<125 micromol/l); moderate impairment, defined as a serum creatinine of 1.5 to 3.0 mg/dL(125-250 micromol/l); and severe renal insufficiency, defined as a serum creatinine greater than 3.0 mg/dL(>250micromol/l).

Complications Associated with Chronic Renal Disease during Pregnancy


Incidence in Percent

Preserved Renal Function
Renal Insufficiency
Complication

Moderate and Severe
Severe
Chronic hypertension
25
30–70
50
Gestational hypertension
20–50
30–50
75
Worsening renal function
8–15
20–43
35
Permanent dysfunction
4–5
10–20
35
Preterm delivery
7
35–60
73
Fetal-growth restriction
8–14
30–37
57
Perinatal mortality
5–14
4–7
5


Management
Frequent prenatal visits are scheduled to monitor blood pressure. Serial serum creatinine values are measured and protein excretion is quantified if indicated. Bacteriuria is treated to decrease the risk of pyelonephritis. Protein-restricted diets are not recommended . Anemia from chronic renal insufficiency responds to recombinant erythropoietin, however, hypertension is a well-documented side effect. Suspected fetal-growth restriction& hypertension .
Follow-Up
At least in some women, pregnancy appears to accelerate chronic renal disease. Theoretically, renal hyperperfusion and increased glomerular blood pressure could accelerate nephrosclerosis.
It seems reasonable to conclude that, in the absence of superimposed preeclampsia or severe hemorrhage and hypovolemia, pregnancy does not usually accelerate renal insufficiency. In women with severe chronic renal insufficiency, however, pregnancy may worsen function.

Dialysis during Pregnancy

Significantly impaired renal function is accompanied by subfertility that may be corrected with chronic hemodialysis or peritoneal dialysis. Not unexpectedly, these pregnancies can be complicated.
Indications for Dialysis
Both hemodialysis and peritoneal dialysis are feasible. If peritoneal dialysis is ongoing, this can be continued during pregnancy. Initiation of dialysis when serum creatinine levels are between 5 and 7 mg/dL. Abrupt volume changes that cause hypotension should be avoided. To accomplish this, dialysis frequency likely is extended to five to six times weekly. Maternal complications are common and include severe hypertension, placental abruption, heart failure, and sepsis.
Pregnancy after Renal Transplantation
They should be in good general health for at least 2 years after transplantation
There should be stable renal function without severe renal insufficiency—serum creatinine <2 mg/dL and preferably <1.5 mg/dL, none to minimal proteinuria, no evidence of graft rejection, and absence of pyelocalyceal distension by urography
Absent or easily controlled hypertension
Drug therapy reduced to maintenance levels.
Concern persists over the possibility of late effects in offspring subjected to immunosuppressive therapy in utero. These include malignancy, germ cell dysfunction, and malformations in the children of the offspring. In addition, cyclosporine is secreted in breast milk, and in at least one instance, it produced therapeutic serum levels in the nursing child.
EFFECT OF PREGNANCY ON RENAL TRANSPLANT
**may have no adverse long term effect
**renal allograft adapt to pregnancy
**about 15% of women develop significant impairment
**about 40% develop proteinuria towards term
EFFECT OF TRANSPLANT ON PREGNANCY
**successful outcome in >90% ,reduced to 70% if complications occur before 28 weeks of gestation
**higher rate of complications in diabetic patients.
Management
Close surveillance is necessary.should managed jointly with nephrologist. Careful monitoring and control of BP is important. Regular assessment of RFT by creatinine clearance and 24 hr protein execretion as wellas S.creatinine and urea is essential. Covert bacteriuria is treated, and if it is recurrent, suppressive treatment is given for the remainder of pregnancy. Serial hepatic enzyme concentrations and blood counts are monitored for toxic effects of azathioprine and cyclosporine. Some recommend measurement of serum cyclosporine levels. Gestational diabetes is more common if corticosteroids are taken. Overt diabetes must be excluded, and glucose tolerance testing is done at approximately 26 weeks. Surveillance for opportunistic infections from herpesvirus, cytomegalovirus, and toxoplasmosis is important because they are more common.
Doses of Immunosuppressive therapy maintained at pre pregnancy levels preferred to be
*Prednisolone <15 mg/day plus either
*azathioprine <2 mg/kg/day
Cyclosporine A 2-4 mg/kg/day
Because of increased incidences of fetal-growth restriction and preterm delivery, vigilant fetal surveillance is indicated .fetal monitoring by regular U/S assessment of growth and Doppler assessment of uterine sand umbilical circulation. Although cesarean delivery is reserved for obstetrical indications, occasionally the transplanted kidney obstructs labor. prophylactic antibiotics given to cover any surgical procedure including episiotomy parentral steroid is necessary to cover labour as with any women on maintenance steroids.
NEONATAL PROBLEMS
Thymic atrophy
Transient leucopenia or thrombocytopenia
Depressed haemopoiesis
Glomerulopathies
The kidney, especially the glomerulus and its capillaries, is subject to a large number and variety of acute and chronic diseases. They may result from a single stimulus such as poststreptococcal glomerulonephritis, or from a multisystem disease such as systemic lupus erythematosus or diabetes.
Acute Nephritic Syndrome
Acute glomerulonephritis may result from any of several causes. They present with hypertension, hematuria, red-cell casts, pyuria, and proteinuria. There are varying degrees of renal insufficiency and salt and water retention, which causes edema, hypertension, and circulatory congestion
Causes of Acute Nephritic Syndrome


Poststreptococcal infection
Subacute bacterial endocarditis
Systemic lupus erythematosus
Antiglomerular basement membrane disease
IgA nephropathy
ANCA small vessel vasculitis
Henoch-Schönlein purpura
Cryoglobulinemia
Membranoproliferative glomerulonephritis
Mesangioproliferative glomerulonephritis

Renal biopsy may be necessary to determine etiology as well as to direct management

IgA Nephropathy
This condition, which is also known as Berger disease, is the most common form of acute glomerulonephritis worldwide. Its primary form is an immune-complex disease. Henoch-Schönlein purpura may be a systemic form of the disease
Effect of Glomerulonephritis on Pregnancy
Whatever the underlying etiology, acute glomerulonephritis has profound effects on pregnancy outcome.
The most common lesions on biopsy were membranous glomerulonephritis, IgA glomerulonephritis, and diffuse mesangial glomerulonephritis. Most of these women had normal renal function, but still overall fetal loss was 25 percent, and the perinatal mortality rate after 28 weeks was 80 per 1000. The worst perinatal outcomes were in women with impaired renal function, early or severe hypertension, and nephrotic-range proteinuria.
Chronic Glomerulonephritis
Chronic disease is characterized by progressive renal destruction over years or decades, eventually producing ESRD. Persistent proteinuria and hematuria commonly accompany a gradual decline in renal function. Microscopically, the renal lesions are categorized as proliferative, sclerosing, or membranous. In most cases, proteinuria, anemia, or elevated creatinine is detected by screening in symptomatic patients, or it is found during evaluation for chronic hypertension. In some women, "typical" preeclampsia-eclampsia does not resolve postpartum, and they subsequently are found to have chronic glomerulonephritis. Its prognosis depends on its etiology, and renal biopsy may be helpful. In some patients, 10 to 20 years may elapse before end-stage renal failure supervenes.

Nephrotic Syndrome

Causes of the Nephrotic Syndrome in Adults


Minimal change disease (MCD) (10–15%): primary idiopathic (most cases), drug-induced (NSAIDs), allergies, viral infections
Focal segmental glomerulosclerosis (FSGS) (33%): viruses, hypertension, reflux nephropathy, sickle-cell disease
Membranous glomerulonephritis (30%): idiopathic (majority), malignancy, infection, connective-tissue diseases
Diabetic nephropathy: most common cause of ESRD
Amyloidosis

Normal amounts of dietary protein of high biological value are encouraged—high-protein diets only increase proteinuria. The incidence of thromboembolism is increased and varies in relation to the severity of hypertension, proteinuria, and renal insufficiency . Although both arterial and venous thrombosis occur, renal vein thrombosis is particularly worrisome. The value, if any, of prophylactic anticoagulation is unclear. Some cases of nephrosis from primary glomerular disease respond to corticosteroid or cytotoxic drug therapy. In most of those cases caused by infection or drugs, proteinuria recedes when the underlying cause is corrected.
Acute Renal Failure
Defined as a rapid decrease in the glomerular filtration rate over minutes to days. Associated mortality depends on its severity and whether dialysis is needed. Today, renal failure is most often associated with severe preeclampsia-eclampsia. Obstetrical hemorrhage, notably placental abruption, alone or in concert with severe preeclampsia, is strongly linked to severe RF & HELLP syndrome
Causes
**infections
*septic abortion
*puerperal sepsis
*acute pyelonephritis(rare)
**Blood loss
*PPH
*abruption
**Volume contraction
*PE
*Eclampsia 6%
*hyperemesis gravidarum
**post PF
*ureteric damage damage or obstruction
**PE
**HELLP SYNDROME
7%have acute renal faiure
*thrombotic thrombocytopenic purpura/hemolytic uremia syndrome(TTP/HUS)
Management
In most women, renal failure develops postpartum, thus management is not complicated by fetal considerations. An acute increase in serum creatinine is usually due to renal ischemia.
Oliguria is an important sign of acutely impaired renal function. In obstetrical cases, both prerenal and intrarenal factors are commonly operative. For example, with total placental abruption, severe hypovolemia is common from massive hemorrhage. Superimposed preeclampsia may cause oliguria.
When azotemia is evident and severe oliguria persists, some form of hemofiltration or dialysis is initiated before marked deterioration occurs. Medication dose adjustments are imperative. Early dialysis appears to reduce the mortality rate appreciably and may enhance the extent of recovery of renal function. With time, renal function usually returns to normal or near normal.
Prevention
Acute tubular necrosis may often be prevented by the following means:
Prompt and vigorous replacement of blood in instances of massive hemorrhage, such as in placental abruption, placental previa, uterine rupture, and postpartum uterine atony
Termination of pregnancies complicated by severe preeclampsia or eclampsia and careful blood replacement if loss is excessive
Close observation for early signs of sepsis syndrome and shock in women with pyelonephritis, septic abortion, chorioamnionitis, or sepsis from other pelvic infections
Avoidance of potent diuretics to treat oliguria before initiating appropriate efforts to ensure that cardiac output is adequate for renal perfusion
Avoidance of vasoconstrictors to treat hypotension, unless pathological vasodilation is unequivocally the cause of the hypotension.
Stone Disease during Pregnancy
Kidney stones develop in 7 percent of women during their lifetime with an average age of onset in the third decade. Calcium salts comprise approximately 80 percent of stones, and up to a half of affected women have polygenic familial idiopathic hypercalciuria. Hyperparathyroidism should be excluded. Although calcium oxalate stones in young nonpregnant women are most common.
Diagnosis
More than 90 percent of pregnant women with nephrolithiasis present with pain & gross hematuria in 23%. Unenhanced helical-CT in pregnancy, citing an average fetal dose to be 700 mrad.
Management
Treatment depends on symptoms and gestational age. Intravenous hydration and analgesics are always given. Half of pregnant women with symptomatic stones have associated infection, which is treated vigorously. Although calculi infrequently cause symptomatic obstruction during pregnancy, persistent pyelonephritis should prompt a search for obstruction due to nephrolithiasis.
In approximately two thirds of women with symptoms, there is improvement with conservative therapy, and the stone usually passes spontaneously. The other third require an invasive procedure such as ureteral stenting, ureteroscopy, percutaneous nephrostomy, transurethral laser lithotripsy, or basket extraction.
Polycystic Kidney Disease
This usually autosomally dominant systemic disease primarily affects the kidneys. The disease is found in 1 in 800 live births and causes approximately 10 percent of end-stage renal disease in the United States.
Renal complications are more common in men than in women, and symptoms usually appear in the third or fourth decade. Flank pain, hematuria, nocturia, proteinuria, and associated calculi and infection are common findings. Hypertension develops in 75 percent, and progression to renal failure is a major problem. Superimposed acute renal failure may also develop from infection or obstruction from ureteral angulation by cyst displacement. Other organs are commonly involved. Hepatic involvement is more common and more aggressive in women than in men. Asymptomatic hepatic cysts coexist in a third of patients with polycystic kidneys.
Polycystic Kidney Disease and Pregnancy
Pregnancy outcome depends on the degree of associated hypertension and renal insufficiency. Upper urinary tract infections are common. Hypertension, including preeclampsia, was more common in women with polycystic kidneys. Pregnancy does not seem to accelerate the natural disease course.