Repeated phlebotomies improve and stabilise renal function in cyanotic nephropathy

Abstract

Patients over 10 years of age with cyanotic congenital heart disease (CCHD) risk developing significant glomerular proteinuria, a condition called cyanotic nephropathy. Even though the pathogenesis of glomerulopathy associated with CCHD is still unclear, a potential mechanism is hyperviscosity-induced decrease in peritubular capillary blood flow leading to an increase in glomerular capillary pressure, in turn resulting in proteinuria. Although angiotensin-converting enzyme (ACE) inhibitors have been traditionally used in the treatment of these patients with cyanotic nephropathy, they may, however, not be well tolerated. Here we present a case of an adult patient with CCHD who could not tolerate an ACE inhibitor but showed improvement and stabilisation of her renal function following treatment with repeated phlebotomies.

BACKGROUND

Phlebotomy, although not routinely used in the management of cyanotic nephropathy, was a viable option that led to improvement and stabilisation of the renal function in our adult patient with cyanotic congenital heart disease (CCHD). As an increasing number of patients with CCHD are now surviving longer into adulthood due to advances in cardiovascular surgery, this case underlines the need for physicians to screen early for proteinuria in these patients and to consider repeated phlebotomies in those CCHD patients with persistent proteinuria despite treatment with an ACE inhibitor.

CASE PRESENTATION

The patient was a 55-year-old female who was cyanotic at birth and diagnosed with pulmonary atresia and ventricular septal defect. She underwent right Blalock-Taussig shunt at age 7 and since then has had multiple episodes of bacterial endocarditis complicated by cerebrovascular accident, pulmonary embolism and pulmonary hypertension.

The patient was noted during one of her recent admissions to our hospital to have 2+ proteinuria on dipstick. There was no associated facial or pedal swelling and no history of smoking, alcohol abuse or illicit drug use. Examination was significant for cyanosis, clubbing and a grade 2/6 harsh systolic murmur along the left sternal border.

INVESTIGATIONS

Significant laboratory findings were 2+ proteinuria with no haematuria or casts, haemoglobin 18 g/dl, serum creatinine 2.4 mg/dl, creatinine clearance 61 ml/min and protein excretion 1.79 g/24 h. Further investigations did not reveal any abnormality known to cause proteinuria.

DIFFERENTIAL DIAGNOSIS

A probable diagnosis of cyanotic nephropathy as a complication of the patient’s longstanding CCHD was considered. However, at this time, the patient was not a good candidate for renal biopsy because of her deteriorating heart function and other overwhelming medical problems.

Differential diagnoses include other causes of adult proteinuria (but these were excluded by the negative work-up in this patient).

TREATMENT

The patient was started on an ACE inhibitor but treatment was limited due to hyperkalaemia. Due to severe polycythaemia, the patient required three series of phlebotomies, which resulted not only in a decrease in haemoglobin to 14.9 g/dl but also a decrease in the creatinine to 1.8 g/dl and a reduction in the urinary protein/creatinine ratio from 7.77 to 3.1 (fig 1).

Figure 1.

Improvement and stabilisation of renal function with repeated phlebotomies in our patient with cyanotic nephropathy.

OUTCOME AND FOLLOW-UP

The patient continued to have repeated phlebotomies as an outpatient and each time she underwent phlebotomy, it improved and stabilised her renal function.

DISCUSSION

More than 70% of CCHD patients over 10 years of age have been reported to develop significant glomerular proteinuria.¹

The structural hallmark of glomerular injury in patients with CCHD has been described as glomerulomegaly, capillary dilatation, thickening of the capillary walls, focal or diffuse proliferation of mesangial cells, and segmental or global glomerulosclerosis.² Although the pathogenesis of glomerulopathy associated with CCHD is still unclear, many potential mechanisms have been described.^3–6 Increased hyperviscosity secondary to polycythaemia is one mechanism that may be responsible for its development and progression.³ The hyperviscosity-induced decrease in peritubular capillary blood flow might lead to an increase in glomerular capillary pressure, in turn resulting in proteinuria.⁴ It has also been postulated that increased shear stress caused by polycythaemic glomerular perfusate induces the release of nitric oxide, resulting in vascular dilatation and glomerulopathy.⁵

Although ACE inhibitors have been shown to be effective in patients with cyanotic nephropathy⁷ by reducing intraglomerular pressure and exerting anti-proteinuric effects through direct influences on glomerular haemodynamics, they may not be well tolerated as in our patient.

Phlebotomy in a CCHD patient will reduce the haematocrit, and the reduced blood viscosity may also exert beneficial effects on hypoxia and glomerular permeability⁸ by reducing postglomerular resistance, thereby decreasing proteinuria^9,10 as in our patient. Haematocrit reduction in our patient was accompanied not only by a fall in proteinuria but also improvement and stabilisation of serum creatinine and the glomerular filtration rate. This observation underlines the importance of a high transcapillary hydraulic pressure gradient in the development of glomerular proteinuria in patients with CCHD.

LEARNING POINTS

• There is a need for early screening for proteinuria in patients with cyanotic congenital heart disease (CCHD).

• Cyanotic nephropathy must be considered in the differential diagnosis of proteinuria in patients with CCHD.

• Repeated phlebotomies as a form of treatment should be considered in those CCHD patients with persistent proteinuria despite treatment with an ACE inhibitor.