Different from previous reported cases of IVC interruption6,7, it is the first case of orthostatic proteinuria attributed to subsequent hemodynamic abnormality of IVC interruption without LRV entrapment. The patient’s LRV received most of infrarenal IVC blood, directly resulting in elevated pressure of LRV and then increasing the pressure of renal venules and efferent arteriole, which caused elevated glomerular capillary hydrostatic pressure and more protein filtering from glomeruli into the primary urine. The pressure of LRV would be more exaggerated due to the calf muscle pump, explaining its postural dependence. Although fixed and reproducible orthostatic proteinuria, this patient had normal serum creatinine and benign renal outcome.
Without longitudinal observation, orthostatic proteinuria is hard to be distinguished from that caused by measuring bias, transient proteinuria after vigorous exercise, and primary or secondary glomerular diseases. After verifying that all quality control (QC) records of urinary microalbumin and total protein were under control, we considered the patient’s highly variant urinary protein was a reflection of her original disease rather than the detection error. This patient’s proteinuria occurred after mild to moderate exercise intensity. Besides, with ACR elevated over 400 times higher than that in first morning void, the degree of fluctuation is much greater than that of postexercise transient proteinuria in healthy man8,9. Although the patient had several risk factors, including obesity, hypertension, and multiple cystic in bilateral kidney that could cause secondary kidney diseases10, the characteristic of proteinuria in these diseases is persistent without extreme daily variance. Besides, her serum tests for secondary kidney diseases, comprising of autoimmune antibodies and monoclonal protein were all negative. Therefore, we excluded the possibility of other kidney diseases.
Orthostatic proteinuria caused by NCS usually happens in slim young individuals and would alleviate after growing up or gaining weight11. The patient was obese and relatively older than those suffered from NCS1. As shown in cross sectional CT and ultrasound, her abdominal fat pad prevented the left renal vein from being compressed by the arteries. These features excluded the possibility of NCS. Less common conditions of NCS comprising pancreatic neoplasms, retroperitoneal tumor, and lordosis etc5. The patient did not have these conditions either. Rarely, Devarajan reported a 40-year-old female whose orthostatic proteinuria was owing to a kink in LRV12, her proteinuria was resolved after donating the left kidney to her kid. The function of local dilation of the LRV in our patient is similar to the kink. To the best of our knowledge, it is the second case of orthostatic proteinuria without LRV entrapment.
The development of IVC, happening between the sixth and eighth gestational weeks, is complicated and could be influenced by the various factors. To date various anatomical variations of IVC have been reported. Double IVC and left ICV are two types that could cause LRV entrapment and orthostatic proteinuria6,13, while our patient did not belong to these conditions.
The prevalence of infra-hepatic interruption of the IVC is about 0.6%6. It might be related with a failure in the development of the right subcardinal-hepatic anastomosis, following the atrophy of the suprarenal IVC. In previous reports, infrarenal IVC would continue as the azygos vein if the IVC is at right side or as the hemiazygos vein if the IVC is at left side. Different from previous reports, the case in this paper had unique venous bypasses, causing dilated bilateral lumbar veins, LRV, azygous and hemizygous vein. Since the degree of venous dilation reflects the proportion of blood pressure, we suspected that most of the blood from lower limbs and pelvic organs drained into the left-side bypass. With the lower limbs muscle pumping effect, more blood would pass through the expanded left-side communicating branch, which exaggerates the proteinuria. The ultrasound’s finding of decreased blood flow velocity at left renal hilum after exercise supported our hypothesis.
Taken together, the atypical age and body weight, and uncommon IVC abnormality as well as nonspecific presentation contributed to the diagnostic odyssey. Lessons we learned from this patient are that for adult patients with postural proteinuria, abnormality of LRV except NCS should be examined carefully, combining the ultrasound and radiography. Besides, figuring out the causal relationship is important, the unexplained but constant proteinuria would lead to anxiety and inappropriate treatment.
Generally, the prognosis of postural proteinuria is excellent via several long-term follow-up cohort study2,14,15. There were cases of kidney biopsy to confirm the pathology16 and interventional or surgical therapy to resolve other complications of NCS 17. Although the proteinuria in this patient was not as self-limited as NCS, she had normal kidney function and daily protein excretion, thus the invasive procedures are not necessary at present.
Management of this unique case were needled, via the department of nephrology, radiology, ultrasound and clinical laboratory working together. We suggested that she should stop other drugs and simply continue the use of losartan, as the angiotensin system blocker had been proved to be effective in animal models and clinical cases18. The follow-up plans included monitoring kidney function, 24-hour urinary protein, and ACR/PCR in first morning excretion and excretion after a fixed-mode activity in a same day. Besides, remain vigilant to the underlying risk of venous thrombosis and kidney impairment, secondary to vessel abnormality is also important.