What is the comprehensive management and treatment approach for a patient with reflex nephropathy, considering potential underlying renal disease, previous surgeries, or injuries?

Reflux Nephropathy: Comprehensive Overview

Definition and Pathophysiology

Reflux nephropathy is a chronic kidney disease caused by vesicoureteral reflux (VUR) leading to renal scarring, and accounts for 5-10% of patients requiring dialysis for end-stage renal failure. 1 The condition develops when urine flows backward from the bladder into the ureters and kidneys, typically during childhood, causing permanent kidney damage through recurrent infections and direct pressure injury.

The pathological hallmark is renal parenchymal scarring that can occur even in radiologically normal kidneys, suggesting past reflux with lateral ureteric orifice insertion. 1 Once scarring develops, three major histological lesions characterize the disease:

• Glomerular hypertrophy correlating with reduced renal function and severe scarring 1
• Focal and segmental glomerulosclerosis (FSGS) correlating with proteinuria 1
• Tubulo-interstitial infiltration predominantly by T4 cells, contributing to glomerular, tubular, and vascular damage 1

Clinical Presentation and Diagnosis

The majority of patients, particularly women, present with urinary tract infections. 2 At initial presentation, expect:

• Hypertension in 8.5% of patients 2
• Proteinuria in 5.1% 2
• Renal insufficiency in 2% 2
• Loin or abdominal pain in 4.8% 2

The disease is often clinically latent and may first manifest during pregnancy through urinary tract infection, proteinuria, hypertension, pre-eclampsia, or acute renal failure. 3

Diagnosis requires intravenous urography and/or DMSA scintigraphy to identify renal scarring patterns. 2 Duplex Doppler scans of ureteric orifices can detect lateral insertion patterns suggesting past reflux even when current imaging appears normal. 1

Disease Progression and Prognosis

Once scarring has occurred, prognosis depends entirely on the severity of initial damage and presence of proteinuria—it is independent of ongoing reflux or infection. 1 This is a critical concept: surgical correction of reflux after scarring has developed does not alter the natural history.

Long-term outcomes at mean age 34 years show:

• Hypertension or antihypertensive therapy requirement in 38% 2
• Proteinuria in 31% 2
• Creatinine clearance <70 mL/min in 24% 2
• Renal insufficiency in 15% 2

Patients with severe bilateral renal parenchymal scarring have significantly higher rates of hypertension, proteinuria, and renal insufficiency. 2 Proteinuria reflects development of glomerulosclerosis and predicts progression to end-stage renal disease. 1

Management Strategy

Blood Pressure Control

Strict control of hypertension is the only widely accepted treatment proven to slow progression. 1 Target blood pressure <130/80 mmHg using ACE inhibitors or ARBs as first-line agents, titrated to maximum approved doses. 4

Proteinuria Management

For patients with proteinuria (ACR ≥300 mg/g or equivalent):

• Initiate ACE inhibitor or ARB therapy immediately 4
• Titrate to maximum tolerated doses regardless of blood pressure if proteinuria persists 4
• Monitor serum creatinine and potassium within 7-14 days of initiation or dose adjustment 4

Dietary Modifications

Implement:

• Low-protein diet (0.6-0.8 g/kg/day) to reduce glomerular hyperfiltration 1
• Dietary salt restriction to <2 g sodium daily 5
• Control of hyperphosphatemia when present 1

Urinary Tract Infection Management

Recurrent pyelonephritis occurs most frequently in patients with persistent vesicoureteral reflux. 3 Maintain high index of suspicion and treat infections aggressively, though infection control does not alter progression once scarring exists. 1

Nephrology Referral Criteria

Refer to specialist kidney care for: 4

• GFR <30 mL/min/1.73 m² (stages G4-G5)
• Consistent significant albuminuria (ACR ≥300 mg/g)
• Progression of CKD (decline in GFR >5 mL/min/1.73 m²/year)
• Hypertension refractory to 4 or more antihypertensive agents
• Persistent hyperkalemia

For stable patients with GFR 30-60 mL/min/1.73 m² without complex features, management by internists or primary care with nephrology consultation (rather than formal ongoing care) may be appropriate. 4

Special Population: Pregnancy

Women with reflux nephropathy should attempt conception before plasma creatinine reaches 0.20 mmol/L (approximately 2.3 mg/dL). 3

For patients with normal or near-normal renal function and absent hypertension at conception:

• Pregnancy is usually successful and uneventful 3
• Urinary tract infections cause frequent morbidity but rarely fetal mortality 3
• Monitor closely for infection, proteinuria, and blood pressure changes 3

For patients with plasma creatinine >0.20-0.22 mmol/L at conception, especially with hypertension, there is high risk of:

• Fetal growth retardation or intrauterine death 3
• Rapid worsening of renal function 3
• Accelerated progression to end-stage renal failure 3

These patients should be clearly advised of the substantial risks to both pregnancy outcome and disease progression. 3

Monitoring Requirements

All patients with reflux nephropathy who have proteinuria, hypertension, or renal insufficiency require regular lifelong follow-up. 2

Monitor at intervals determined by disease severity:

• Serum creatinine and eGFR every 3-6 months for stable disease 4
• Urinary albumin-to-creatinine ratio every 3-6 months 4
• Blood pressure at every visit 4
• Serum potassium when on ACE inhibitors/ARBs 4
• Screen for urinary tract infections based on symptoms 2

For patients with eGFR <30 mL/min/1.73 m², consider interdisciplinary CKD care programs, which have demonstrated improved outcomes including reduced hospitalizations and higher quality of life in the CanPREVENT trial. 4

Key Clinical Pitfalls

The most critical error is assuming that correction of reflux will prevent progression once scarring has occurred—it will not. 1 Management must focus on the consequences of existing damage rather than the reflux itself.

Do not delay ACE inhibitor/ARB therapy waiting for blood pressure elevation—these agents provide renoprotection independent of blood pressure effects in proteinuric patients. 4

Avoid NSAIDs entirely as they worsen kidney function and interfere with sodium excretion. 6

Do not underestimate the risk of rapid deterioration during pregnancy in patients with moderate renal impairment—counsel appropriately before conception. 3