Abstract:
Introduction. Renal calculi have been plaguing humanity since the advent of civilization. The
majority of kidney stones consist of calcium oxalate, followed by calcium phosphate, uric acid,
cysteine, and struvite stones. Many factors influence the development of a stone including diet,
genetics, environment, and comorbid conditions.
Aim of the study. To describe a hypothesis for the initial events leading to urinary stones. A
biomechanical perspective on Randall's plaque formation through form and function
relationships is applied to functional units within the kidney, we have termed the 'medullopapillary
complex' - a dynamic relationship between intratubular and interstitial mineral
aggregates.
Materials and methods. A complete research was performed to examine the existing literature
on the anatomical and physiological relationships in the renal medulla and papilla. Sectioned
human renal medulla with papilla from radical nephrectomy specimens were imaged using a
high resolution micro X-ray computed tomography. The location, distribution, and density of
mineral aggregates within the medullo-papillary complex were identified.
Results. Mineral aggregates were seen proximally in all specimens within the outer medulla of
the medullary complex and were intratubular. Distal interstitial mineralization at the papillary tip
corresponding to Randall's plaque was not seen until a threshold of proximal mineralization was
observed. Mineral density measurements suggest varied chemical compositions between the
proximal intratubular (330 mg/cm3) and distal interstitial (270 mg/cm3) deposits. A review of the
literature revealed distinct anatomical compartments and gradients across the medullo-papillary
complex that supports the empirical observations that proximal mineralization triggers distal
Randall's plaque formation.
Conclusions. Randall's plaques may not be the entire explanation for lithogenic phenomena,
they do play an important role in a subset of patients with calcium oxalate stones, whose
incidence has been increasing in recent decades. The early stone event is initiated by intratubular
mineralization of the renal medullary tissue leading to the interstitial mineralization that is
observed as Randall's plaque. We base this novel hypothesis on a multiscale biomechanics
perspective involving form and function relationships, and empirical observations. Additional
studies are needed to validate this hypothesis.
