Sucrose nephropathy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]
Synonyms and keywords: Osmotic nephropathy, IVIg induced nephropathy, hypertonic solution induced nephropathy
Overview
Sucrose containing infusions have been associated with acute kidney injury specifically in high risk patients with preexisting renal impairment. The clinical syndrome is seen mostly in patients treated with intravenous immunoglobulins (IVIg) stabilized with sucrose.
Historical Perspective
Sucrose nephropathy was first described in 1942 by Rigdon et al following administration of intravenous hypertonic sucrose solution to patients.[1] This model later became the basis of osmotic nephrosis, a term used to describe histologic findings of vacuolization of renal tubules after administration of intravenous hypertonic solutions including sucrose, hydroxyethyl starch, dextrans, or contrast media.[2] Osmotic nephropathy as a disease entity gained attention as a possible cause for contrast induced nephropathy, and fairly recently as a side effect of high-dose immunoglobulin therapy. Acute renal failure was not initially described as an adverse effect of IVIg therapy after its introduction in 1952. The first case of osmotic nephropathy due to IVIg therapy was reported in 1987.[3] Since then several other cases have been described.
Pathophysiology
The mechanism of osmotic nephropathy was initially described with the use of intravenous sucrose with histological renal findings showing proximal renal tubular cell swelling and tubular lumen occlusion.[1] With the advent of IVIg manufactured with sucrose stabilizers, sucrose nephropathy resurfaced as a cause for kidney injury. Various sugars have been used as stabilizers to decrease aggregate formation between IVIg molecules including sucrose, glucose, sorbitol and maltose. However, more than 90% of cases of IVIg associated nephropathy have been linked to sucrose-stabilized immunoglobulins, the most widely used preparation in the United States.[4] Usually, sucrose-stabilized preparations contain comparatively large quantities of sucrose (1.67 mg/ml).[5] This filtered sucrose is supposedly taken up by renal tubular cells via pinocytosis. Since renal tubular cells do not disaccharidase they accumulate in the cells. The vesicles then coalesce to form vacuoles.[6] Tubular cell swelling then leads to luminal narrowing and subsequent acute kidney injury.
In general, reports of renal impairment with sucrose-free IVIGs are relatively rare. Other stabilizing agents are probably better tolerated since they can be actively metabolized by the renal tubular cells. It has even been shown that patients with previous AKI secondary to IVIg therapy tolerate sucrose-free IVIg well.[7]
Epidemiology and Demographics
Between 1987 and 2009, approximately 115 cases of sucrose-containing IVIg induced kidney injury have been reported in the literature.
Risk Factors
Clinical trends showed that older age, diabetes, intravascular volume depletion especially in the setting of diuretic use and preexistent renal disease may predispose to the development of acute kidney injury in patients on sucrose-stabilized IVIg.
Natural History, Complications and Prognosis
Clinically, the response to these hyperosmotic solutions can be very variable and at times being completely asymptomatic. Renal impairment may occur within a few days after IVIg infusion and is usually anuric and resolves over several weeks.[8] Chronic renal failure is extremely rare with only one reported case.[9]
Treatment
IVIg should be discontinued with the first sign of kidney injury. If IVIg therapy is stopped early on, more than 80% of patients recover kidney function. Treatment is usually supportive similar to other forms of acute kidney injury until the patient recovers renal function. One third of patients may require temporary hemodialysis.[10]
Prevention
Urine output and creatinine clearance should be closely monitored after initiation of sucrose containing IVIg therapy. Dilution of preparations to decrease sucrose load and proper hydration may also help decrease the risk of renal injury but studies on primary prevention are lacking.
References
- ↑ 1.0 1.1 Renal lesions following the intravenous injection of a hypertonic solution of sucrose: a clinical and experimental study. Rigdon RH, Cardwell ES. s.l. : Archives of Internal Medicine, 1942, Vol. 69, pp. 678-690.
- ↑ Dickenmann M, Oettl T, Mihatsch MJ (2008). "Osmotic nephrosis: acute kidney injury with accumulation of proximal tubular lysosomes due to administration of exogenous solutes". Am J Kidney Dis. 51 (3): 491–503. doi:10.1053/j.ajkd.2007.10.044. PMID 18295066.
- ↑ Barton JC, Herrera GA, Galla JH, Bertoli LF, Work J, Koopman WJ (1987). "Acute cryoglobulinemic renal failure after intravenous infusion of gamma globulin". Am J Med. 82 (3 Spec No): 624–9. PMID 3103443.
- ↑ Gelfand EW (2006). "Differences between IGIV products: impact on clinical outcome". Int Immunopharmacol. 6 (4): 592–9. doi:10.1016/j.intimp.2005.11.003. PMID 16504921.
- ↑ Dantal J (2013). "Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk". Am J Nephrol. 38 (4): 275–284. doi:10.1159/000354893. PMID 24051350.
- ↑ Schwartz SL, Johnson CB (1971). "Pinocytosis as the cause of sucrose nephrosis". Nephron. 8 (3): 246–54. PMID 4344404.
- ↑ Haskin JA, Warner DJ, Blank DU (1999). "Acute renal failure after large doses of intravenous immune globulin". Ann Pharmacother. 33 (7–8): 800–3. PMID 10466908.
- ↑ Sati HI, Ahya R, Watson HG (2001). "Incidence and associations of acute renal failure complicating high-dose intravenous immunoglobulin therapy". Br J Haematol. 113 (2): 556–7. PMID 11380432.
- ↑ Ahsan N (1998). "Intravenous immunoglobulin induced-nephropathy: a complication of IVIG therapy". J Nephrol. 11 (3): 157–61. PMID 9650125.
- ↑ Cayco AV, Perazella MA, Hayslett JP (1997). "Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature". J Am Soc Nephrol. 8 (11): 1788–94. PMID 9355083.