The present work is a reassessment of Study 1 and Study 2, the only published work on the use of random spot urine P/C ratio to estimate 24-hour proteinuria in SLE GN patients. There have been numerous reports on the use of random spot urine P/C ratio to estimate 24-hour proteinuria in non-SLE CKD [5
]. However, it cannot be assumed that the results of proteinuria testing in non-SLE CKD will be the same as that of SLE GN [22
]. Relevant differences include that SLE GN patients are overwhelmingly female, and generally smaller than non-SLE CKD. This results in lower urine creatinine excretion rates in the SLE cohorts. In addition, SLE GN patients are more likely to manifest inflammation, which lowers serum albumin by increasing catabolism [22
]. Also, data from SLE mouse models suggest that the renal tubular catabolism of filtered proteins is less than that of non-SLE models of kidney disease [22
Study 1 concluded that random spot urine P/C ratio was unreliable in estimating 24-hour P/C ratio. Study 2, using Bland-Altman and receiver operator curve analyses, concluded that random spot urine P/C ratio was a reliable estimate of 24-hour proteinuria.
The present work shows that Study 1 and Study 2 are, in fact, in good agreement. Over the P/C ratio range 0.5–3.0, both Study 1 and Study 2 document that random spot urine P/C ratio is an unreliable estimate of 24-hour urine P/C ratio. The degree of unreliability is large and, in individual patients, likely would lead to important diagnostic and therapeutic errors. For example, a BILAG Category A proteinuric flare is indicated when 24-hour proteinuria increases from ≤0.2 to >1 g/day [7
]. From inspection of figure , it is clear that random spot urine P/C ratios would have difficulty detecting whether a proteinuric flare had occurred. As shown in figure , at a 24-hour P/C ratio of about 1.0, random spot P/C ratio testing produces values that range from nearly 0 to >3.0.
Using the same line of reasoning, it is clear that random spot urine P/C ratio testing would have difficulty identifying whether other types of BILAG Category A proteinuric flare had occurred (24-hour proteinuria >1.0 g increasing by 100%, or newly documented 24-hour proteinuria of >1.0 g) [7
], or whether BILAG Category B proteinuric flare had occurred (24-hour urine protein that has increased from >1 g by 50% but less than 100%) [7
Random spot P/C ratio would also be unreliable in detecting proteinuria flares in SLE GN patients whose baseline proteinuria is in the nephrotic range. For example, as shown in figure , for a patient whose 24-hour P/C ratio is about 4.0, random spot P/C would provide values as low as 2.0 to as high as 6.0. The latter value would be a BILAG Category B flare, the former value would not.
The present work, however, cannot be used to determine the extent to which using random spot urine P/C ratio would confound the accurate management of SLE GN because the present work did not specifically examine random spot P/C ratio and 24-hour urine P/C ratio in relationship to flares. That will require a separate study.
The greater reliability of an intended 24-hour collection to estimate 24-hour P/C ratio can be expected because the P/C ratio of an intended 24-hour collection is the integrated mean of multiple spot urine P/C ratios, which are intrinsically ‘bouncy’ even under conditions that maximize proteinuria stability [5
]. An intended 24-hour urine that is at least 50% complete averages those bounces to provide a reliable estimate of the true 24-hour urine P/C ratio.
Recent work suggests that urine collection periods that are longer than spot collections but shorter than intended 24-hour collections may also reliably estimate 24-hour proteinuria. These include overnight collections [23
] or collections over about 08.00 to 14.00 or 12.00 to 24.00 h [24
]. The caveat with using shorter urine collection periods to assess proteinuria in individual patients is that minor changes in the patients’ usual routine could importantly influence the protein or creatinine content of the shorter collection. Such changes could include nocturia, diet (salt or protein intake), medication timing, exercise, posture, body temperature (e.g., fever) [4
], or whether the urine contains semen [25