Chronic Kidney Disease and its Sequelae within the Cobb Collection: Osteological Manifestations and Clinical Record of Evidence
Amanda D. Strong, B.S. 1,2
Uzoamaka Nwaogwugwu, M.D .3
Fatimah Jackson, Ph.D. 1,2
Christopher Cross, M.S. 1,4
1W. Montague Cobb Research Laboratory, Howard University
2Department of Biology, Howard University
3Department of Medicine, College of Medicine, Howard University
4Department of Anatomy, Howard University
Chronic Kidney Disease (CKD) has plagued the African American (AA) community as a frequent result of severe hypertension and diabetes, both diseases that may be instigated by environmental factors or hereditary factors such as genetics. CKD is an ailment that causes a dangerous imbalance of vital minerals and ions, and can cause waste to build up throughout the major organs of the body. In contrast to its prevalence, there is an underrepresentation of CKD when participating in cadaver dependent research; this is the result of major consequences of CKD, such as cardiovascular or neurological symptoms being pronounced the cause of death. The Cobb Research Laboratory’s (CRL) investigation within chronic kidney disease will involve the examination of cadaver skeletons whose deaths have been notably caused by CKD. With the information gathered from these investigations, the CRL team is optimistic for anatomical clues left behind by the disease in the hopes of diagnosing other unknown cases within the Cobb Collection for further research. With the findings of more cases it will be possible to examine the genes that are linked to CKD as well as find explanations that could assist in research on the preventative progression of the disease.
In the United States, the AA community constitutes approximately 13% of the entire population, yet 32% of all patients receiving treatment for kidney failure are AA,1 this leads to an overall kidney failure rate that is over three times larger than that of our Caucasian counterparts. It has also been shown that AAs require dialysis or transplantation at younger ages.6,7 Chronic kidney disease most often leads to end-stage renal disease (ESRD) in which the kidneys can no longer function at the level necessary to remove all of the waste and excess water from the body.2 AAs have greater incidence rates of ESRD at each decade of life compared with any other racial/ethnic group.6,7 The likelihood for the development of chronic kidney disease is determined by the relationship and interactions between genes and the environment.3 It is key to understand both the genetic and environmental factors so that novel treatments and therapies can be developed. Most importantly, understanding the underrepresentation of CKD and why it plagues our community will aid in developing the preventative measures needed to improve our statistical status on the matter. Socio-environmental, behavioral, biomedical, and predisposing factors all work together towards particular health outcomes. Once all taken into consideration, real progress can and will be made.
As reported by the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) and displayed in Figure 1, African-Americans (red circles) have the highest occurrence of ESRD incidents and well as the highest exponential increase since the year of 1980. In second lead, incidents in Native Americans (blue diamonds) began to rise up until 1999 when a decrease began. Asians (yellow squares) and Caucasians (green triangles) have shown the slightest increase in comparison with the others. Compared to the other ethnic groups analyzed and to the overall average of those groups, AA’s have, and have always had, the highest rate of CKD incidents.
African Americans and Native Americans share many social environmental stressors that may have aided in their correlation up until 1999. The quickly accelerating progression of the disease has often be attributed to risk factors such as diabetes, hypertension and obesity; however, this has not been able to explain the elevated rate of CKD progressing into ESRD among AAs and other groups with low socioeconomic status.8 Unfortunately, the consequences of the social environment is too often over-looked as a contributing element. Through behavioral science studies, it has been established that there are psychological and physiological consequences dependent on the environment in which one works and lives.9,10 Social environmental stressors such as poverty and discrimination are proven to adverse the bodies psychological functioning as well as prompt response in regards to the nervous and vascular systems; these complications place individuals at greater risk for developing CKD and cause a lesser ability to prevent the progression towards ESRD.8 From Figure 3, it can be seen that social environmental factors are the beginning of a chain of risk factors that can contribute to other high risk factors such as psychosocial and behavioral that lead to negative effects in pathophysiological mechanisms. Social issues such as economic struggle and discrimination often lead to psychological manifests of anxiety, depression and stress. Alone, the psychological state can impact the physiological functions of the body; however, the situation is heightened double-fold when these psychological factors instigate poor habits such as drug use, poor diet and lowered physical activity. Many studies have focused on the effect of racial discrimination and institutionalized racism.
It has been suggested that the excess risks for chronic diseases such as CKD among groups such as African Americans (and Native Americans) are a function of economic deprivation. However, racial disparities in the prevalence and progression of kidney disease continue to persist even when the socioeconomic position at the individual and community level is improved and stable.11,12,13 The main concern given by Figure 1 is in regards to the continuation of an exponential rise in ESRD in African-Americans that differentiates them from others of same or lower socioeconomical status. These results lead us to examine the genetic factors as the only key to understanding why the difference among AAs occurs. It is a fact that AAs14 have the highest risk associated with family history, as do Native Americans15 and Hispanic Americans;16 however, it is observed in case studies across the United States that AAs are the only racial group to have a nine-fold higher risk of developing ESRD if they already have a first degree family member on dialysis.17 Some studies have concluded racially variable susceptibility rate is due to familial clustering of those with CKD in certain racial groups,3 but other research has indicated a correlation among AA individuals who have a mutation at the location of the PKD1 gene. 3,18 From newer studies a positive correlation between similar genetic mutations and familial clustering has been found, thus combining the two previous theories.
In Kidney International studies, it was shown that the location of the PKD1 gene mutation is directly correlated with the severity of renal disease and the onset of ESRD.18 In studies regarding rodent renal failure a correlation was noticed in the Rf-1 gene, the rodent analog of the human chromosome10 To assess any possible linkage between markers on chromosome10 and ESRD potential, a linkage analysis was performed in African American sibling-pairs. It was shown that in AAs with nondiabetic etiologies of ESRD, there was strong suggestive evidence for linkage on chromosome 10p, specifically.3 Curiously, this is near the D10S1435 marker that is confirmed to have a consistent presence in diabetic families.19 For AA families with a history of type 2 diabetic nephropathy, a genome wide scan on sibling pairs showed evidence for linkage on chromosomes 3q, 10q, and 18q.20 Notably, the type 1 diabetic nephropathy locus was at the 3q peak in the chromosome. 21 Studying the close proximity of these chromosomal markers and loci may help to explain the continuous relation between diabetes and renal disease beyond the physiological level and allow for a genetic perspective. This information is extremely useful in determining the cause of CKD underrepresentation in the AA community. Essentially, there is a considerable amount of evidence that supports family history of renal disease, as well as familial clustering of ESRD, as contribution to the pathogenesis of chronic kidney failure.3 Identification of causative elements located within the genome may enlighten the development of innovative gene therapies.3
According to Dr. Uzoamaka Nwaogwugwu, MD and DaVita expert, renal osteodystrophy is the most common bone disease associated with kidney failure. This disease causes significant imbalances in calcium, parathyroid hormone, phosphorus and activated vitamin D. The condition further develops to affect the balance of osteoclast and osteoblast development and production.  When the calcium levels in the blood begin to drop a significant amount, the body begins to over activate the parathyroid glands to produce the parathyroid hormone. This hormone will begin to extract calcium from the skeletal system and into the bloodstream in order regain calcium equilibrium. As the calcium is being stripped from the bones they begin to weaken and the texture becomes chalky, rather than the natural sturdy form.  Secondly, kidney disease causes an extremely high amount of phosphorous levels in the blood. Because calcium and phosphorous share a symbiotic relationship, the body will begin to draw calcium from the bones into the blood to create equilibrium between calcium and phosphorous.  Of course, this causes the same side effect of low blood calcium and diminishes the bone. The kidneys serve an ultimately vital function of activating the vitamin D that courses through our blood to form calcitriol. Calcitriol is acts to assist the body in absorbing calcium and maintaining normal parathyroid hormone levels.  Unfortunately, when the kidneys begin to fail, they are no longer able to convert vitamin D into calcitriol and the body is no longer able to absorb dietary calcium properly. Again, the body attempts to fulfill its calcium need by stealing from within the bones.
The typical symptoms for degradation of the bone include: bone and joint pain, bone deformation and fractures, as well as poor mobility.  In the case of this research, bone deformation is the key component. When having suffered from long-term renal failure or chronic kidney disease, evidence of the disease is left behind on the skeletal structure. Osteodystrophy, osteomalacia, uremia and metabolic bone disease all alter the visual integrity of the bone. Bone lesions, porousness, thinning or thickening, and the abnormal curving of the bone are all potential signs that the skeletal system was being robbed of essential minerals and ions.
In Figure 4, the abnormal curvature and slight protrusion towards the tips of the bone can be seen. When describing osteomalacia, Dr. Nwaogwugwu described how the bone matrix weakens and the bone begins to flare up towards the joints, where majority of the damage occurs. Figure 5 shows the lack of mineral density near the joints when suffering from renal osteodystrophy. Renal osteodystrophy has been viewed using an X-ray, even when being viewed as a defleshed cadaver. The symptoms most suitable for observation in the laboratory are related to lesion formation. Lesions can be seen on the bone without using tools, however, this can cause an issue when attempting to differentiate natural deterioration from mechanical damage due to processing. Fortunately, an X-ray picture of the bone lesions can reveal its true nature and will not be confused with mechanical damage.
Methods and Procedures
Extensive research was done on what types of osteological symptoms would be present in order to truly piece together our analysis of cadaver skeletons from the Cobb collection. The beginning step was to completely review the digital Cobb Collection files, with the assistance of our director, Dr. Fatimah Jackson, for all patients whose cause of death was related to kidney malfunction or kidney disease. The exact cause of death, age, race and body number was noted. It was then that some of the noted bodies were pulled with guidance of our assistant curator and student of anatomy, Christopher Cross. The entire anatomy of a carefully chosen, defleshed cadaver was laid out on the laboratory table and reconfigured for organization and easy access, as shown in Figure 8.
Beginning with the bones that survive the most tension and pressure through the lifetime, as well as the highly sensitive joints, we attempted to find signs of lesioning, porosity and abnormal morphology on the femurs. This task became difficult as we faced questions that had not yet posed an issue. During the retrieval of many skeletons from the African Burial Ground (New York), many of the bones were damaged through mechanical digging and treating.
As can be seen in Figure 9 and in Figure 10, it is difficult to categorize the damage on the bone under a specific cause. While it is possible that the damage to the bone could be the result of deterioration, it could also be damage inflicted from machinery or rough handling during transportation.
Figure 11 is an example of how normal differences in midsagittal skeletal structure can be mistaken for the thinning or improper curving of the bone. The left femur, on the bottom of the figure, appears thinner with slightly more curvature than its left counter part. It is expected for the skeletal anatomy to differ slightly when analyzing midsagittal pieces. The question that arises is whether or not this difference is significant enough to note it as an osteopathic symptom. In the lab, we also noticed a difference in the texture and color of the two bones, yet determination of the cause was not entirely clear. All fragments in question were photographically captured for future comparison.
Ultimately, we were not able to determine as much as had been anticipated through the physical laboratory analysis due to the uncertain observations; however, the flaws in our expectations have been led us to new venues, methods, and resources to continue our hunt for answers. To eliminate misperception between natural deterioration of bone and mechanical damage done to it, we have proposed x-ray scanning. By using a radiographically produced image (Figure 5 and Figure 7), it would allow us to see beyond the outer surface of the bone and deeper into its matrix; for example, dark areas within the bone matrix will indicate significant deterioration, as in renal osteodystrophy whereas patch-like spots on the bone will indicate bone lesions have formed. Utilizing the Howard University Hospital Critical Image and Photo department will allow the W. Montague Cobb Research laboratory access to x-ray machines as well as bone biopsy processes. Bone biopsies will allow us to insure consistent results by confirming osteopathic symptoms that appear similar also have similar chemical and molecular makeup. This will be helpful in proving the exact mineral composition that results from these pathological processes. Along with Dr. Nwaogwugwu, we hope to make a connection with the Howard University Hospital Pathology department in order to gain a more complete understanding of the bone pathologies in this focus. To assist in differentiating what is appropriate for expected anatomical difference in the bone versus significant bone curvature or loss (Figure 11), the Howard University Hospital Osteology department will be able to analyze measurements taken in the lab as well as photographs.
In the proceeding research, we will use the information gain to find more cases of osteopathic symptoms representing CKD in the Cobb Collection. Specifically, we will do this by examining defleshed cadavers that have causes of death most often associated with CKD (i.e., diabetes, cardiovascular disease, nuerological disorders). Not only will this add more sources to our research, but will allow for the W. Montague Cobb Research Laboratory to have a more detailed record for causes of death. Having an extended collection of defleshed cadavers specifically marked for CKD would also allow us to collect DNA samples from a variety of sources in order to analyze the genes and attempt to find common markers and genetic clues. Potentially, finding a common genetic factor amongst all CKD cases in the Cobb Collection could allow for a starting point for gene therapies. We can then extend the research to verify whether CKD is prominent in a certain sex, age or lifestyle (i.e., profession, family size) within the AA community. By comparing location of deaths, a crude idea of how the social environment impacted the progression of CKD can be composed. Being that the Cobb Collection contains African remains dating back to the 17th century, we also hope to find a positive correlation between rising CKD levels and time spent in what is now the United States. We are hoping to find clues that will allow us to hypothesize in regards to why AA specifically have developed predispositions for chronic disease that is not common of our ancestry.
In all, this research is guided towards to the awareness and understanding of how and why chronic kidney disease affects the African American population at an exponential rate. Our research could potentially serve as a foundation of knowledge for a disease that is highly neglected on the preventative and treatment level in our community. If we improve our understanding of what factors place African Americans at risk for chronic kidney disease, we will be better equipped to avoid those scenarios as preventative measure.
We would like to thank our director, Dr. Fatimah Jackson, PhD, for allowing us to be apart of the amazing experience of the W. Montague Research Cobb Laboratory. We would also like to thank our curator, Christopher Cross, MS, for his helpful instruction when analyzing the anatomy of the cadaver skeletons in the Cobb Collection. Finally, I would like to thank Matthew Calhoun for his ideas and constructive conversation toward the research.
"African Americans and Kidney Disease." The National Kidney Foundation. N.p., Apr. 2014. Web.
Miller, Scott, MD, and David Zieve, MD, MHA. "End-stage Kidney Disease: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. U.S. National Library of Medicine, 2 Oct. 2013. Web.
"Kidney Disease Statistics for the United States." Kidney Diseases Statistics for the United States. National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), June 2012. Web.
"3 Risk Factors and Causes of Chronic Kidney Disease." Australian Institute of Health and Welfare. N.p., n.d. Web.
Hsu C-Y, Lin F, Vittinghoff E, et al. Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States. J Am Soc Nephrol. 2003;14:2902–2907.
Tareen N, Zadshir A, Martins D, et al. Chronic kidney disease in African American and Mexican American populations. Kidney Int. 2005;68(supplement 97):S137–S140.
Bruce, Marino A., Bettina M. Beech, Mario Sims, Tony N. Brown, Sharon B. Wyatt, Herman A. Taylor, David R. Williams, and Errol Crook. "Social Environmental Stressors, Psychological Factors, and Kidney Disease." Journal of Investigative Medicine : The Official Publication of the American Federation for Clinical Research. U.S. National Library of Medicine, 18 Feb. 2010. Web.
Fremont A, Bird C. Social and psychological factors, physiological processes, and physical health. In: Bird C, Conrad P, Fremont A, editors. Handbook of Medical Sociology. Upper Saddle, NJ: Prentice Hall; 2000. pp. 334–352.
Seeman T, Mcewan B. Impact of social environment characteristics on neuroendocrine regulation. Psychosom Med. 1996;58:459–471.
Norris K, Nissenson AR. Race, gender, and socioeconomic disparities in CKD in the United States. J Am Soc Nephrol. 2008;19(7):1261–1270.
Tarver-Carr ME, Powe NR, Eberhardt MS, et al. Excess risk of chronic kidney disease among African Americans versus white subjects in the united states: a population-based study of potential explanatory factors. J Am Soc Nephrol. 2002;13:2363–2370.
Volkova N, McClellan W, Klein M, et al. Neighborhood poverty and racial differences in ESRD incidence. J Am Soc Nephrol. 2008;19(2):356–364.
FREEDMAN, BI, SOUCIE, JM, MCCLELLAN, WM: Family history of end-stage renal disease among incident dialysis patients. J Am Soc Nephrol 1997 8:1942–1945.
PETTITT, DJ, SAAD, MF, BENNETT, PH, et al: Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non–insulin-dependent) diabetes mellitus. Diabetologia 1990 33:438–443, 10.1007/BF00404096.
PUGH, J: Diabetic nephropathy and end-stage renal disease in Mexican Americans. Blood Purif 1996 14:286–292.
FREEDMAN, BI, SPRAY, BJ, TUTTLE, AB, BUCKALEW, VM: The familial risk of end-stage renal disease in African Americans. Am J Kidney Dis 1993 21:387–393.
ROSSETTI, S, BURTON, S, STRMECKI, L, et al: The position of the polycystic kidney disease 1(PDK1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol 2002 13:1230–1237, 10.1097/01.ASN.0000013300.11876.37.
IYENGAR, SK, FOX, KA, SCHACHERE, M, et al: Linkage analysis of candidate Loci for end-stage renal disease due to diabetic nephropathy. J Am Soc Nephrol 2003 14(7 Suppl 2):S195–S201, 10.1097/01.ASN.0000070078.66465.55.
BOWDEN, DW, COLICIGNO, CJ, LANGEFELD, CD, et al: A genome scan for diabetic nephropathy in African Americans. Kidney Int 2004 66:1517–1526.
MAGISTRONI, R, HE, N, WANG, K, ANDREW, R, et al: Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2003 14:1164–1174, 10.1097/01.ASN.0000061774.90975.25.
"Renal Osteodystrophy - Bone Disease and Kidney Failure." - DaVita. N.p., n.d. Web.
Combe, Liv. "How Your Body Uses Phosphorus." Healthline. N.p., 21 Nov. 2014. Web.
"Osteomalacia." Generic Look. N.p., n.d. Web.
"Renal Osteodystrophy | Mineral Bone Disorder - Signs Symptoms Diagnosis Treatment." Medindia. N.p., n.d. Web.
"Museum of London - Cross Bones Burial Ground Photographs." Museum of London - Cross Bones Burial Ground: Centre for Human Bioarchaeology. N.p., 2005. Web.
"Orthopedic Teaching: Bone Lesions Case 2 Answer." Bone Lesions Case 2 Answer : : Feinberg School of Medicine: Northwestern University. Northwestern University Feinburg School of Medicine, n.d. Web